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1.
Braz. j. med. biol. res ; 53(12): e9615, 2020. tab, graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1132513

ABSTRACT

The sympathetic nervous system (SNS) plays a fundamental role in the pathophysiology of cardiovascular diseases, including primary arterial hypertension. In this study, we aimed to investigate whether the expression of the rate-limiting enzyme in catecholamine synthesis, tyrosine hydroxylase (TH), and the β2-adrenergic receptor (β2-AR) in immune cells from peripheral blood, reflect central SNS activity in spontaneously hypertensive rats (SHR). TH expression in the lower brainstem and adrenal glands and β2-AR expression in the lower brainstem were analyzed by western blot analyses. In the leukocytes, TH and β2-AR expression was evaluated by flow cytometry before and after chronic treatment with the centrally-acting sympathoinhibitory drug clonidine. Western blot analyses showed increased TH and β2-AR expression in the lower brainstem and increased TH in adrenal glands from SHR compared to normotensive Wistar Kyoto rats (WKY). Lower brainstem from SHR treated with clonidine presented reduced TH and β2-AR levels, and adrenal glands had decreased TH expression compared to SHR treated with vehicle. Flow cytometry showed that the percentage of leukocytes that express β2-AR is higher in SHR than in WKY. However, the percentage of leukocytes that expressed TH was higher in WKY than in SHR. Moreover, chronic treatment with clonidine normalized the levels of TH and β2-AR in leukocytes from SHR to similar levels of those of WKY. Our study demonstrated that the percentage of leukocytes expressing TH and β2-AR was altered in arterial hypertension and can be modulated by central sympathetic inhibition with clonidine treatment.


Subject(s)
Animals , Rats , Hypertension/drug therapy , Rats, Inbred SHR , Rats, Inbred WKY , Sympathetic Nervous System , Tyrosine 3-Monooxygenase , Blood Pressure , Receptors, Adrenergic, beta-2 , Leukocytes
2.
Braz. j. med. biol. res ; 52(6): e8009, 2019. graf
Article in English | LILACS | ID: biblio-1001539

ABSTRACT

The progression of myocardial injury secondary to hypertension is a complex process related to a series of physiological and molecular factors including oxidative stress. This study aimed to investigate whether moderate-intensity exercise (MIE) could improve cardiac function and oxidative stress in spontaneously hypertensive rats (SHRs). Eight-week-old male SHRs and age-matched male Wistar-Kyoto rats were randomly assigned to exercise training (treadmill running at a speed of 20 m/min for 1 h continuously) or kept sedentary for 16 weeks. Cardiac function was monitored by polygraph; cardiac mitochondrial structure was observed by scanning electron microscope; tissue free radical production was measured using dihydroethidium staining. Expression levels of SIRT3 and SOD2 protein were measured by western blot, and cardiac antioxidants were assessed by assay kits. MIE improved the cardiac function of SHRs by decreasing left ventricular systolic pressure (LVSP), and first derivation of LVP (+LVdP/dtmax and −LVdP/dtmax). In addition, exercise-induced beneficial effects in SHRs were mediated by decreasing damage to myocardial mitochondrial morphology, decreasing production of reactive oxygen species, increasing glutathione level, decreasing oxidized glutathione level, increasing expression of SIRT3/SOD2, and increasing activity of superoxide dismutase. Exercise training in SHRs improved cardiac function by inhibiting hypertension-induced myocardial mitochondrial damage and attenuating oxidative stresses, offering new insights into prevention and treatment of hypertension.


Subject(s)
Animals , Male , Rats , Blood Pressure/physiology , Oxidative Stress/physiology , Hypertension/physiopathology , Mitochondria, Heart/physiology , Cardiomyopathies/prevention & control , Physical Conditioning, Animal/physiology , Rats, Inbred SHR , Rats, Inbred WKY , Superoxide Dismutase/physiology , Microscopy, Electron, Scanning , Disease Models, Animal , Cardiomyopathies/physiopathology , Cardiomyopathies/diagnostic imaging
3.
Article in Chinese | WPRIM | ID: wpr-774567

ABSTRACT

The aim of this study was to observe the effect of baicalin on the growth state of attention deficit hyperactivity disorder animal model and its regulation on Ca MKⅡand ERK1/2.In the present study,a total of 40 SHR rats were randomly divided into model group,methylphenidate hydrochloride group,and low,medium,and high dose baicalin groups,with 8 rats in each group.Eight WKYrats were selected as a normal control group.The methylphenidate hydrochloride group(0.07 g·L~(-1))and the low(3.33 g·L~(-1)),medium(6.67 g·L~(-1)),and high dose(10 g·L~(-1))baicalin groups received corresponding drugs by gavage administration according to the body weight(0.015 m L·g~(-1)),while the normal group and the model group received the same volume of normal saline by gavage.Thegavage administration lasted for 4 weeks,twice a day.The body weight of the rats and the amount of remaining feed were weighed daily,and the growth state of the rats was statistically evaluated weekly.Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structures.The Ca MKⅡand ERK1/2 protein and mRNA expression levels were detected with Western blot and Real-time PCR methods,respectively.RESULTS: showed that baicalin did not affect the normal eating and weight gain of rats,and the weight gain of rats was even more significant than that in the normal group(P<0.05).In the study of its effects on Ca MKⅡand ERK1/2 protein expression in rat synaptosomes,the expression of both proteins in each drug-administered group was higher than that in the model group(P<0.05);besides,the expression levels of Ca MKⅡand ERK1/2 protein were significantly increased in both baicalin high dose group and the methylphenidate hydrochloride group(P<0.05).The relative expression of Ca MKⅡand ERK1/2 mRNA in synaptosome was detected by PCR.The results showed that medium and high doses of baicalin and methylphenidate hydrochloride significantly increased the relative expression of Ca MKⅡand ERK1/2 mRNA in synaptosomes of SHR rats(P<0.05).In conclusion,baicalin does not affect the normal growth and development of SHR rats,so it is safe for administration.Both baicalin and methylphenidate hydrochloride could up-regulate the relative expression of Ca MKⅡand ERK1/2 in mRNA and protein,and the pharmacodynamic stability of baicalin is in a dose-dependent manner to certain extent.


Subject(s)
Animals , Attention Deficit Disorder with Hyperactivity , Disease Models, Animal , Flavonoids , Intracellular Signaling Peptides and Proteins , MAP Kinase Signaling System , Protein-Serine-Threonine Kinases , Rats , Rats, Inbred SHR , Rats, Inbred WKY
4.
Acta Physiologica Sinica ; (6): 395-404, 2019.
Article in Chinese | WPRIM | ID: wpr-777174

ABSTRACT

The present study was designed to examine whether Ramipril (an inhibitor of angiotensin-converting enzyme) affected spontaneous hypertension-induced injury of cerebral artery by regulating connexin 43 (Cx43) expression. Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were randomly divided into WKY, WKY + Ramipril, SHR, and SHR + Ramipril groups (n = 8). The arterial pressure was monitored by the tail-cuff method, and vascular function in basilar arteries was examined by pressure myography. Hematoxylin-eosin (HE) staining was used to show vascular remodeling. The expression and distribution of Cx43 was determined by using immunofluorescence and immunohistochemistry analysis. The protein and mRNA levels of Cx43 were examined by Western blot and real-time PCR analysis, respectively. The results showed that chronic Ramipril treatment significantly attenuated blood pressure elevation (P < 0.01, n = 8) and blood vessel wall thickness in SHR (P < 0.01, n = 8). The cerebral artery contraction rate in the SHR group was higher than that in the WKY group (P < 0.05, n = 8). The cerebral artery contraction rate in the SHR + Ramipril group was lower than that in the SHR group (P < 0.05, n = 8). Pretreatment with 2-APB (Cx43 non-specific blocker) or Gap26 (Cx43 specific blocker) significantly decreased the vasoconstriction rate, while pretreatment with AAP10 (Cx43 non-specific agonist) significantly increased the vasoconstriction in the SHR + Ramipril group (P < 0.05, n = 8). In addition, the expression of Cx43 mRNA and protein in cerebral arteries of SHR group was higher than that of WKY group (P < 0.05, n = 8). The mRNA and protein expression of Cx43 in cerebral arteries of SHR + Ramipril group was significantly lower than that of SHR group (P < 0.05, n = 8). These results suggest that Ramipril can down-regulate the expression of Cx43 mRNA and protein in cerebral arterial cells of SHR, lower blood pressure, promote vasodilation, and improve arterial damage and vascular dysfunction caused by hypertension.


Subject(s)
Animals , Blood Pressure , Cerebral Arteries , Metabolism , Connexin 43 , Metabolism , Hypertension , Drug Therapy , Ramipril , Pharmacology , Random Allocation , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Vascular Remodeling
5.
Acta Physiologica Sinica ; (6): 505-513, 2019.
Article in English | WPRIM | ID: wpr-777161

ABSTRACT

Activation of peripheral respiratory chemoreceptors provokes respiratory and cardiovascular reflexes, providing a novel understanding of pathogenic mechanism of hypertension. Here we hypothesize that activation of peripheral respiratory chemoreceptors by hypoxia causes enhanced cardiorespiratory activity in conscious spontaneously hypertensive rats (SHRs). Using whole body plethysmography in combination with radio telemetry, pulmonary ventilation, arterial blood pressure and heart rate were examined in SHRs and Wistar-Kyoto (WKY) rats. We found that exposure to hypoxia induced greater increases in tidal volume and minute ventilation volume in SHRs compared to WKY rats. In addition, hypoxia caused a robust increase in arterial blood pressure and heart rate in SHRs relative to WKY counterparts. After carotid body denervation, the hypoxic ventilatory response was significantly decreased in both SHRs and WKY rats, but without significant difference between the two strains; moreover, the differences of arterial blood pressure and heart rate changes during hypoxic exposure were statistically insignificant between SHRs and WKY rats. It is concluded that hypoxia remarkably potentiates cardiorespiratory activity in the SHRs, suggesting an enhanced sensitivity of carotid bodies to hypoxia.


Subject(s)
Animals , Blood Pressure , Heart Rate , Hypertension , Hypoxia , Rats , Rats, Inbred SHR , Rats, Inbred WKY
6.
Psychiatry Investigation ; : 558-564, 2019.
Article in English | WPRIM | ID: wpr-760953

ABSTRACT

OBJECTIVE: Synaptic vesicle mobilization and neurite outgrowth regulation molecules were examined in modulation of effects of methylphenidate (MPH) in Spontaneous Hypertensive Rats (SHRs), a model for attention-deficit hyperactivity disorder (ADHD). METHODS: We compared the changes in the protein expression level of Cyclin dependent kinase 5 (Cdk5) and molecular substrates of Cdk5; tropomyosin receptor kinase B (TrkB), syntaxin 1A (STX1A) and synaptosomal-associated protein 25 (SNAP25). Comparisons were made in prefrontal cortex of vehicle (distilled water i.p. for 7 days)-treated SHRs, vehicle-treated Wistar Kyoto Rats (WKYs) and MPH (2 mg/kg i.p. for 7 days) treated SHRs. RESULTS: The Cdk5 level of vehicle-treated SHRs was significantly decreased compared to the Cdk5 level of vehicle-treated WKY rats, but was restored to the expression level of vehicle-treated WKYs in MPH-treated SHR. The ratio of p25/p35 was significantly decreased in MPH-treated SHR compared to vehicle-treated SHR. Moreover, TrkB, STX1A and SNAP25 of vehicle-treated SHRs were significantly decreased compared to vehicle-treated WKY rats, but were restored to the expression level of vehicle-treated WKYs in MPH-treated SHR. CONCLUSION: The results show that Cdk5, TrkB, STX1A, and SNAP25 were involved in the modulation of MPH effects in prefrontal cortex of SHRs and play important role in treatment of ADHD.


Subject(s)
Animals , Cyclin-Dependent Kinase 5 , Methylphenidate , Neurites , Phosphotransferases , Prefrontal Cortex , Rats , Rats, Inbred WKY , Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins , Synaptic Vesicles , Synaptosomal-Associated Protein 25 , Syntaxin 1 , Tropomyosin , Water
7.
Arq. bras. cardiol ; 110(3): 263-269, Mar. 2018. tab, graf
Article in English | LILACS | ID: biblio-888040

ABSTRACT

Abstract Background: Alterations in the structure of resistance vessels contribute to elevated systemic vascular resistance in hypertension and are linked to sympathetic hyperactivity and related lesions in target organs. Objective: To assess the effects of exercise training on hemodynamic and autonomic parameters, as well as splenic arteriolar damages in male Wistar Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR). Methods: Normotensive sedentary (WKYS) and trained (WKYT) rats, and hypertensive sedentary (SHRS) and trained (SHRT) rats were included in this study. After 9 weeks of experimental protocol (swimming training or sedentary control), arterial pressure (AP) and heart rate (HR) were recorded in freely moving rats. We assessed the autonomic control of the heart by sympathetic and vagal autonomic blockade. Morphometric analyses of arterioles were performed in spleen tissues. The statistical significance level was set at p < 0.05. Results: Resting bradycardia was observed in both trained groups (WKYT: 328.0 ± 7.3 bpm; SHRT: 337.0 ± 5.2 bpm) compared with their respective sedentary groups (WKYS: 353.2 ± 8.5 bpm; SHRS: 412.1 ± 10.4 bpm; p < 0.001). Exercise training attenuated mean AP only in SHRT (125.9 ± 6.2 mmHg) vs. SHRS (182.5 ± 4.2 mmHg, p < 0.001). The WKYT showed a higher vagal effect (∆HR: 79.0 ± 2.3 bpm) compared with WKYS (∆HR: 67.4 ± 1.7 bpm; p < 0.05). Chronic exercise decreased sympathetic effects on SHRT (∆HR: -62.8 ± 2.8 bpm) in comparison with SHRS (∆HR: -99.8 ± 9.2 bpm; p = 0.005). The wall thickness of splenic arterioles in SHR was reduced by training (332.1 ± 16.0 µm2 in SHRT vs. 502.7 ± 36.3 µm2 in SHRS; p < 0.05). Conclusions: Exercise training attenuates sympathetic activity and AP in SHR, which may be contributing to the morphological improvement of the splenic arterioles.


Resumo Fundamento: Alterações na estrutura dos vasos de resistência contribuem para elevar a resistência vascular sistêmica na hipertensão, estando ligadas à hiperatividade simpática e lesões em órgãos-alvo. Objetivo: Avaliar os efeitos do treinamento físico nos parâmetros hemodinâmicos e autônomos, assim como as lesões arteriolares esplênica em ratos machos Wistar Kyoto (WKY) e espontaneamente hipertensos (SHR). Métodos: Ratos normotensos sedentários (WKYS) e treinados (WKYT), e ratos hipertensos sedentários (SHRS) e treinados (SHRT) foram incluídos neste estudo. Após nove semanas de aplicação do protocolo experimental (treinamento de natação ou controle sedentário), registraram-se a pressão arterial (PA) e a frequência cardíaca (FC) dos ratos em movimento livre. Avaliamos o controle autônomo do coração através de bloqueio autônomo simpático e vagal. Análises morfométricas das arteríolas esplênicas foram realizadas. Adotou-se o nível de significado estatístico de p < 0,05. Resultados: Observou-se bradicardia de repouso nos dois grupos treinados (WKYT: 328,0 ± 7,3 bpm; SHRT: 337,0 ± 5,2 bpm) em comparação aos seus respectivos grupos sedentários (WKYS: 353,2 ± 8,5 bpm; SHRS: 412,1 ± 10,4 bpm; p < 0,001). O treinamento físico atenuou a PA média apenas no grupo SHRT (125,9 ± 6,2 mmHg vs. 182,5 ± 4,2 mmHg no SHRS; p < 0,001). O grupo WKYT mostrou maior efeito vagal (∆FC: 79,0 ± 2,3 bpm) em comparação ao grupo WKYS (∆FC: 67,4 ± 1,7 bpm; p < 0,05). Exercício crônico diminuiu os efeitos simpáticos em SHRT (∆FC: -62.8 ± 2.8 bpm) em comparação a SHRS (∆FC: -99,8 ± 9,2 bpm; p = 0,005). A espessura da parede das arteríolas esplênicas nos SHR foi reduzida pelo treinamento (332,1 ± 16,0 µm2 nos SHRT vs. 502,7 ± 36,3 µm2 nos SHRS; p < 0,05). Conclusões: O treinamento físico atenua a atividade simpática e a PA em SHR, o que pode contribuir para melhorar a morfologia das arteríolas esplênicas.


Subject(s)
Animals , Male , Physical Conditioning, Animal/physiology , Splenic Artery/physiopathology , Splenic Artery/pathology , Sympathetic Nervous System/physiopathology , Vascular Resistance/physiology , Arterial Pressure/physiology , Hypertension/physiopathology , Physical Conditioning, Animal/methods , Arterioles/physiopathology , Rats, Inbred SHR , Rats, Inbred WKY , Reference Values , Time Factors , Reproducibility of Results , Treatment Outcome , Exercise Therapy/methods , Heart Rate/physiology , Hypertension/therapy
8.
Braz. j. med. biol. res ; 51(11): e7338, 2018. tab, graf
Article in English | LILACS | ID: biblio-951725

ABSTRACT

Hypertensive renal damage generally occurs during the middle and late stages of hypertension, which is typically characterized by proteinuria and renal inflammation. Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been widely used for therapy of arterial hypertension and cardiovascular diseases. However, the protective effects of captopril on hypertension-induced organ damage remain elusive. The present study was designed to explore the renoprotective action of captopril in spontaneously hypertensive rats (SHR). The 6-week-old male SHR and age-matched Wistar-Kyoto rats were randomized into long-term captopril-treated (34 mg/kg) and vehicle-treated groups. The results showed that in SHR there was obvious renal injury characterized by the increased levels of urine albumin, total protein, serum creatinine, blood urea nitrogen, renal inflammation manifested by the increased mRNA and protein expression of inflammatory factors including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase, and enhanced nuclear factor-κB (NF-κB) activation. Captopril treatment could lower blood pressure, improve renal injury, and suppress renal inflammation and NF-κB activation in SHR rats. In conclusion, captopril ameliorates renal injury and inflammation in SHR possibly via inactivation of NF-κB signaling.


Subject(s)
Animals , Male , Rats , Proteinuria/prevention & control , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Captopril/therapeutic use , NF-kappa B/adverse effects , Hypertension/drug therapy , Nephritis/prevention & control , Antihypertensive Agents/therapeutic use , Proteinuria/etiology , Rats, Inbred SHR , Rats, Inbred WKY , Signal Transduction , Hypertension/complications , Nephritis/etiology
9.
Article in Chinese | WPRIM | ID: wpr-773783

ABSTRACT

OBJECTIVES@#Investigate the influence of benazepril and amlodipine on the expression of secretin (PZ) and somatostatin (SS) in spontaneously hypertensive rats (SHR).@*METHODS@#Forty-five SHRs (14 weeks old, male) were randomly assigned into 3 groups (=15):SHR group, Benazepril group (which was given benazepril 0.90 mg·kg·d) and Amlodipine group (SHRs were given amlodipine 0.45 mg· kg·d), taking WistarKyoto(WKY) as normal control (=15), meanwhile, rats in SHR group and WKY group were given the same volume of distilled water. After 8 weeks of intervention, the expression of protein and mRNA of PZ in duodenum and SS in sinuses ventriculi was detected by enzyme-linked immunoassay and RT-PCR.@*RESULTS@#After 8 weeks of intervention, compared with the WKY group, the expression of protein and mRNA of PZ in duodenum and SS in sinuses ventriculi was increased significantly in SHR group (<0. 05). Compared with SHR group, the expression of PZ in duodenum and SS in sinuses ventriculi was decreased significantly in Benazepril group and Amlodipine group (<0.05). Compared with Benazepril group, in Amlodipine group the expression of PZ mRNA in duodenum and SS mRNA in sinuses ventriculi was decreased more significantly (<0.05).@*CONCLUSIONS@#The regulation disorder of PZ in duodenum and SS in sinuses ventriculi exists in SHR. The antihypertensive effect of benazepril and amlodipine may be realized by regulating the expression of PZ and SS, while the regulation of amlodipine is more obvious than benazepril.


Subject(s)
Amlodipine , Pharmacology , Animals , Antihypertensive Agents , Pharmacology , Benzazepines , Pharmacology , Blood Pressure , Hypertension , Drug Therapy , Male , Random Allocation , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Secretin , Metabolism , Somatostatin , Metabolism
10.
Article in English | WPRIM | ID: wpr-715441

ABSTRACT

OBJECTIVE: Whether blood-brain barrier (BBB) disruption induced by chronic spontaneous hypertension is associated with beta-amyloid (Aβ) accumulation in the brain remains poorly understood. The purpose of this study was to investigate the relationship between BBB disruption and Aβ influx and accumulation in the brain of aged rats with chronic spontaneous hypertension. MATERIALS AND METHODS: Five aged spontaneously hypertensive rats (SHRs) and five age-matched normotensive Wistar-Kyoto (WKY) rats were studied. The volume transfer constant (Ktrans) obtained from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to evaluate BBB permeability in the hippocampus and cortex in vivo. The BBB tight junctions, immunoglobulin G (IgG), Aβ, and amyloid precursor protein (APP) in the hippocampus and cortex were examined with immunohistochemistry. RESULTS: As compared with WKY rats, the Ktrans values in the hippocampus and cortex of the SHRs increased remarkably (0.316 ± 0.027 min−1 vs. 0.084 ± 0.017 min−1, p < 0.001 for hippocampus; 0.302 ± 0.072 min−1 vs. 0.052 ± 0.047 min−1, p < 0.001 for cortex). Dramatic occludin and zonula occludens-1 losses were detected in the hippocampus and cortex of SHRs, and obvious IgG exudation was found there. Dramatic Aβ accumulation was found and limited to the area surrounding the BBB, without extension to other parenchyma regions in the hippocampus and cortex of aged SHRs. Alternatively, differences in APP expression in the hippocampus and cortex were not significant. CONCLUSION: Blood-brain barrier disruption is associated with Aβ influx and accumulation in the brain of aged rats with chronic spontaneous hypertension. DCE-MRI can be used as an effective method to investigated BBB damage.


Subject(s)
Alzheimer Disease , Amyloid , Animals , Blood-Brain Barrier , Brain , Hippocampus , Hypertension , Immunoglobulin G , Immunohistochemistry , Magnetic Resonance Imaging , Methods , Occludin , Permeability , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Tight Junctions
11.
Acta cir. bras ; 32(5): 388-395, May 2017. tab, graf
Article in English | LILACS | ID: biblio-837711

ABSTRACT

Abstract Purpose: To evaluate DNA damage levels in pregnant rats undergoing a treadmill exercise program. Methods: Wistar Kyoto rats were allocated into two groups (n= 5 animals/group): non-exercise and exercise. The pregnant rats were underwent an exercise protocol on a treadmill throughout pregnancy. Exercise intensity was set at 50% of maximal capacity during maximal exercise testing performed before mating. Body weight, blood pressure and glucose levels, and triglyceride concentration were measured during pregnancy. At day 10 post-natal, the animals were euthanized and maternal blood samples were collected for DNA damage. Results: Blood pressure and glucose levels and biochemical measurements showed no significant differences. Increased DNA damage levels were found in exercise group compared to those of non-exercise group (p<0.05). Conclusion: The exercise intensity protocol used in the study might have been exhaustive leading to maternal increased DNA damage levels, demonstrating the relevance of an adequate protocol of physical exercise.


Subject(s)
Animals , Female , DNA Damage/physiology , Exercise Test/adverse effects , Physical Conditioning, Animal , Rats, Inbred WKY , Blood Glucose/analysis , Blood Pressure/physiology , Body Weight/physiology , Pregnancy , Random Allocation , Comet Assay/methods , Models, Animal , Exercise Test/standards , Fetal Viability/physiology , Animals, Newborn/physiology
12.
Article in English | WPRIM | ID: wpr-812076

ABSTRACT

Angiotensin II (Ang II) is involved in endothelium injury during the development of hypertension. Tribulus terrestris (TT) is used to treat hypertension, arteriosclerosis, and post-stroke syndrome in China. The present study aimed to determine the effects of aqueous TT extracts on endothelial injury in spontaneously hypertensive rats (SHRs) and its protective effects against Ang II-induced injury in human umbilical vein endothelial cells (HUVECs). SHRs were administered intragastrically with TT (17.2 or 8.6 g·kg·d) for 6 weeks, using valsartan (13.5 mg·kg·d) as positive control. Blood pressure, heart rate, endothelial morphology of the thoracic aorta, serum levels of Ang II, endothelin-1 (ET-1), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured. The endothelial injury of HUVECs was induced by 2 × 10 mol·L Ang II. Cell Apoptosisapoptosis, intracellular reactive oxygen species (ROS) was assessed. Endothelial nitric oxide synthase (eNOS), ET-1, SOD, and MDA in the cell culture supernatant and cell migration were assayed. The expression of hypertension-linked genes and proteins were analyzed. TT decreased systolic pressure, diastolic pressure, mean arterial pressure and heart rate, improved endothelial integrity of thoracic aorta, and decreased serum leptin, Ang II, ET-1, NPY, and Hcy, while increased NO in SHRs. TT suppressed Ang II-induced HUVEC proliferation and apoptosis and prolonged the survival, and increased cell migration. TT regulated the ROS, and decreased mRNA expression of Akt1, JAK2, PI3Kα, Erk2, FAK, and NF-κB p65 and protein expression of Erk2, FAK, and NF-κB p65. In conclusion, TT demonstrated anti-hypertensive and endothelial protective effects by regulating Erk2, FAK and NF-κB p65.


Subject(s)
Angiotensin II , Metabolism , Animals , Antihypertensive Agents , Apoptosis , Blood Pressure , Endothelium, Vascular , Metabolism , Human Umbilical Vein Endothelial Cells , Humans , Hypertension , Drug Therapy , Genetics , Metabolism , Male , NF-kappa B , Genetics , Metabolism , Nitric Oxide Synthase Type III , Genetics , Metabolism , Oxidative Stress , Plant Extracts , Proto-Oncogene Proteins c-akt , Genetics , Metabolism , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Reactive Oxygen Species , Metabolism , Tribulus , Chemistry
13.
National Journal of Andrology ; (12): 110-119, 2017.
Article in Chinese | WPRIM | ID: wpr-812801

ABSTRACT

Objective@#To screen lentiviral vectors carrying siRNA which can specifically down-regulate the gene expression of the sphingosine-1-phosphate receptor 3 (S1PR3) in the corpus cavernosum smooth muscle (CCSM) cells of rats with spontaneous hypertension (SHT) and investigate the influence of the vectors on the signaling pathways of ROCK1, ROCK2 and eNOS in the CCSM cells of SHT rats.@*METHODS@#Using the S1PR3 mRNA sequence of the rat as an interfering target, we designed and synthesized three pairs of siRNA sequences (siRNA1, 2 and 3) targeting S1PR3 and one pair of negative control, and then constructed and packaged them into lentiviral vectors. We cultured the CCSM cells of SHT and Wistar-Kyoto (WKY) rats in vitro and randomly divided them into groups A (SHT untransfected control), B (SHT transfected and carrying negative control virus), C (SHT transfected and carrying siRNA1 targeting S1PR3), D (SHT transfected and carrying siRNA2 targeting S1PR3), E (SHT transfected and carrying siRNA3 targeting S1PR3), and F (WKY untransfected control). With the multiplicity of infection (MOI) = 60, we transfected the CCSM cells of the SHT rats with the lentiviral vector and then determined the expression of the green fluorescent protein (GFP) as well as the mRNA and protein expressions of S1PR3, ROCK1, ROCK2 and eNOS in the CCSM cells of the SHT and WKY rats by RT-PCR and Western blot.@*RESULTS@#Gene sequencing proved the successful construction of the lentiviral vector. The transfection efficiency of the CCSM cells of the rats was >80% in groups B, C, D and E. Compared with group A, the mRNA and protein expressions of S1PR3, ROCK1 and ROCK2 exhibited no significant difference in group B but were remarkably decreased in groups C, D, E and F (P0.05) but remarkably lower than those in group F (P0.05) but markedly increased in groups A, B, C and D (P< 0.05), while those of eNOS remarkably decreased in groups A, B, C, D and E (P< 0.05).@*CONCLUSIONS@#The three constructed lentiviral vectors carrying siRNA targeting different loci of the S1PR3 gene could significantly inhibit the expression of S1P3 as well as RhoA/Rho kinase signaling pathways in the CCSM cells of SHT rats, and the vector carrying siRNA3 exhibited the highest inhibitory effect.


Subject(s)
Animals , Down-Regulation , Gene Expression , Genetic Vectors , Green Fluorescent Proteins , Metabolism , Lentivirus , Genetics , Male , Myocytes, Smooth Muscle , Metabolism , Nitric Oxide Synthase Type III , Metabolism , Penis , Metabolism , RNA, Messenger , RNA, Small Interfering , Genetics , Metabolism , Random Allocation , Rats , Rats, Inbred WKY , Receptors, Lysosphingolipid , Genetics , Metabolism , Signal Transduction , Sphingosine-1-Phosphate Receptors , Transfection , rho-Associated Kinases , Metabolism
14.
Article in Chinese | WPRIM | ID: wpr-297244

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of baicalin on synaptosomal adenosine triphosphatase (ATPase) and lactate dehydrogenase (LDH) and its regulatory effect on the adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway in rats with attention deficit hyperactivity disorder (ADHD).</p><p><b>METHODS</b>A total of 40 SHR rats were randomly divided into five groups: ADHD model, methylphenidate hydrochloride treatment (0.07 mg/mL), and low-dose (3.33 mg/mL), medium-dose (6.67 mg/mL), and high-dose (10 mg/mL) baicalin treatment (n=8 each). Eight WKY rats were selected as normal control group. Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structure. Colorimetry was used to measure the activities of ATPase and LDH in synaptosomes. ELISA was used to measure the content of AC, cAMP, and PKA.</p><p><b>RESULTS</b>Compared with the normal control group, the ADHD model group had a significant reduction in the ATPase activity, a significant increase in the LDH activity, and significant reductions in the content of AC, cAMP, and PKA (P<0.05). Compared with the ADHD model group, the methylphenidate hydrochloride group and the medium- and high-dose baicalin groups had a significant increase in the ATPase activity (P<0.05), a significant reduction in the LDH activity (P<0.05), and significant increases in the content of AC, cAMP, and PKA (P<0.05). Compared with the methylphenidate hydrochloride group, the high-dose baicalin group had significantly greater changes in these indices (P<0.05). Compared with the low-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P<0.05); the medium- and high-dose baicalin groups had a significant reduction in the LDH activity (P<0.05) and significant increases in the content of AC, cAMP, and PKA (P<0.05). Compared with the medium-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P<0.05).</p><p><b>CONCLUSIONS</b>Both methylphenidate hydrochloride and baicalin can improve synaptosomal ATPase and LDH activities in rats with ADHD. The effect of baicalin is dose-dependent, and high-dose baicalin has a significantly greater effect than methylphenidate hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating the AC/cAMP/PKA signaling pathway.</p>


Subject(s)
Adenosine Triphosphatases , Metabolism , Adenylyl Cyclases , Physiology , Animals , Attention Deficit Disorder with Hyperactivity , Drug Therapy , Cyclic AMP , Physiology , Cyclic AMP-Dependent Protein Kinases , Physiology , Flavonoids , Pharmacology , Therapeutic Uses , L-Lactate Dehydrogenase , Metabolism , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Signal Transduction , Synaptosomes , Chemistry
15.
Article in Chinese | WPRIM | ID: wpr-297182

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of baicalin on the behavioral characteristics of rats with attention deficit hyperactivity disorder (ADHD), and to provide a basis for further research on baicalin in the treatment of ADHD.</p><p><b>METHODS</b>A total of 40 SHR rats were randomly divided into model group, methylphenidate hydrochloride (MPH) group, and low-, medium-, and high-dose baicalin groups, with 8 rats in each group. Eight WKY rats were selected as normal control group. The rats in the MPH group (0.07 mg/mL) and the low- (3.33 mg/mL), medium- (6.67 mg/mL), and high-dose (10 mg/mL) baicalin groups were given the corresponding drugs (1.5 mL/100 g) by gavage twice a day, and those in the normal control group and the model group were given an equal volume of normal saline by gavage twice a day. The course of treatment was 4 weeks for all groups. The open field test was performed to observe total moving distance and average moving speed on day 0 of experiment and at 7, 14, 21, and 28 days after gavage and to evaluate the control effects of drugs on hyperactivity and impulsive behavior. The Morris water maze test was used to observe the latency, time spent in the target quadrant, and number of platform crossings and to evaluate the effects of drugs on attention.</p><p><b>RESULTS</b>The open field test showed that the model group and the drug treatment groups had a significantly longer total moving distance and a significantly higher average moving speed than the normal control group on day 0 (P<0.05). On day 7, the MPH group had significant reductions in total moving distance and average moving speed compared with the model group (P<0.05). On day 14, the MPH group and the high-dose baicalin group had significant reductions in total moving distance and average moving speed compared with the model group (P<0.05). The data on days 21 and 28 showed that compared with the model group, the low-, medium-, and high-dose baicalin groups had gradual reductions in total moving distance and average moving speed (P<0.05). The water maze test showed that compared with the model group, the MPH group and the medium- and high-dose baicalin groups had a significantly longer time spent in the target quadrant (P<0.05), and the MPH group and the high-dose baicalin group had a significantly higher proportion of the moving distance in the target quadrant in total moving distance (P<0.05). The high-dose baicalin group had the highest number of platform crossings among all groups (P<0.05).</p><p><b>CONCLUSIONS</b>Both baicalin and MPH can regulate the motor ability and learning and memory abilities of SHR rats with ADHD and thus control the core symptoms of ADHD, i.e., hyperactivity, impulsive behavior, and inattention. Baicalin exerts its effect in a dose-dependent manner, and high-dose baicalin has the most significant effect, but compared with MPH, it needs a longer time to play its therapeutic effect.</p>


Subject(s)
Animals , Attention Deficit Disorder with Hyperactivity , Drug Therapy , Psychology , Behavior, Animal , Dose-Response Relationship, Drug , Flavonoids , Therapeutic Uses , Male , Maze Learning , Motor Activity , Rats , Rats, Inbred SHR , Rats, Inbred WKY
16.
Arq. bras. cardiol ; 106(3): 201-209, Mar. 2016. tab, graf
Article in English | LILACS | ID: lil-777100

ABSTRACT

Abstract Background: Resistance training (RT) has been recommended as a non-pharmacological treatment for moderate hypertension. In spite of the important role of exercise intensity on training prescription, there is still no data regarding the effects of RT intensity on severe hypertension (SH). Objective: This study examined the effects of two RT protocols (vertical ladder climbing), performed at different overloads of maximal weight carried (MWC), on blood pressure (BP) and muscle strength of spontaneously hypertensive rats (SHR) with SH. Methods: Fifteen male SHR ENT#091;206 ± 10 mmHg of systolic BP (SBP)ENT#093; and five Wistar Kyoto rats (WKY; 119 ± 10 mmHg of SBP) were divided into 4 groups: sedentary (SED-WKY) and SHR (SED-SHR); RT1-SHR training relative to body weight (~40% of MWC); and RT2-SHR training relative to MWC test (~70% of MWC). Systolic BP and heart rate (HR) were measured weekly using the tail-cuff method. The progression of muscle strength was determined once every fifteen days. The RT consisted of 3 weekly sessions on non-consecutive days for 12-weeks. Results: Both RT protocols prevented the increase in SBP (delta - 5 and -7 mmHg, respectively; p > 0.05), whereas SBP of the SED-SHR group increased by 19 mmHg (p < 0.05). There was a decrease in HR only for the RT1 group (p < 0.05). There was a higher increase in strength in the RT2 (140%; p < 0.05) group as compared with RT1 (11%; p > 0.05). Conclusions: Our data indicated that both RT protocols were effective in preventing chronic elevation of SBP in SH. Additionally, a higher RT overload induced a greater increase in muscle strength.


Resumo Fundamentos: O treinamento de força (TF) tem sido recomendado como tratamento não farmacológico para hipertensão arterial moderada. Apesar do papel importante que a intensidade do exercício desempenha sobre a prescrição do treinamento, ainda não há nenhum dado avaliando os efeitos da intensidade do TF sobre a hipertensão arterial grave (HAG). Objetivo: Este estudo analisou os efeitos de dois protocolos do TF(subida em escada vertical), realizados com diferentes sobrecargas do peso máximo carregado (PMC), sobre a pressão arterial (PA) e a força muscular de ratos espontaneamente hipertensos (SHR) com HAG. Métodos: Quinze SHR machos (206 ± 10 mmHg de PA sistólica (PAS)) e cinco ratos Wistar Kyoto (WKY; 119 ± 10 mmHg de PAS) foram divididos em 4grupos:sedentários: (SED-WKY) e SHR (SED-SHR); treinados: TF1-SHR conforme o peso corporal (~40% do PMC); e TF2-SHR conforme o teste de PMC (~70% do PMC). Foram coletadas medidas de PAS e a frequência cardíaca (FC) semanalmente usando o método de pressão arterial caudal. A progressão da força muscular foi determinada a cada 15 dias. O TF consistiu de 3 sessões semanais em dias não consecutivos durante 12 semanas. Resultados: Os dois protocolos de TF preveniram o aumento da PAS(respectivamente, delta - 5 e -7 mmHg; p > 0, 05), enquanto que a PAS do grupo SED-SHR aumentou em 19 mmHg (p < 0, 05). Houve queda na FC apenas para o grupo TF1 (p < 0, 05). Foi observado um aumento mas significativo de força no grupo do protocolo TF2 (140%; p < 0, 05) em comparação com o TF1 (11%; p>0, 05). Conclusões: Nossos dados indicam que ambos os protocolos de TF foram efetivos na prevenção da elevação crônica da PAS na HAG. Além disso, sobrecargas maiores de TF induziram a um maior aumento de força muscular.


Subject(s)
Animals , Male , Hypertension/physiopathology , Physical Conditioning, Animal/physiology , Resistance Training , Blood Pressure/physiology , Body Weight/physiology , Heart Rate/physiology , Models, Animal , Muscle Stretching Exercises , Muscle Strength/physiology , Rats, Inbred SHR , Rats, Inbred WKY
17.
Acta Physiologica Sinica ; (6): 12-18, 2016.
Article in Chinese | WPRIM | ID: wpr-331688

ABSTRACT

The aim of the present study was to investigate the effects of ketamine, imipramine, and ketamine plus imipramine on chronic depression-like behaviors of Wistar Kyoto (WKY) rats and underlying mechanism. Six-week-old Wistar rats were used as normal control. WKY rats, depression model animal, were injected intraperitoneally with ketamine (1 week, replaced with saline in 2(nd) week), imipramine (2 weeks), or ketamine in combination with imipramine. The depression-like behaviors were assessed by sucrose preference and forced swimming tests. Protein expressions of β form of calcium/calmodulin-dependent protein kinase type II (βCaMKII) and membrane fraction of glutamate receptor 1 (GluR1) were measured in corresponding brain tissue with Western blot. The results showed that, compared with Wistar rats, WKY rats exhibited decreased sucrose preference and extended immobility time. Ketamine alone did not affect depression-like behaviors of WKY, whereas imipramine or its combination with ketamine could significantly decrease the immobility time. Compared with Wistar rats, WKY rats showed up-regulated levels of βCaMKII and membrane GluR1 protein expressions in habenula, and down-regulated level of membrane GluR1 protein expressions in the prefrontal cortex. Imipramine or its combination with ketamine could reverse these changes of protein expressions in WKY rats. There was no difference in reversing effect between imipramine and its combination with ketamine. Ketamine alone did not affect the βCaMKII and membrane GluR1 protein expressions in the habenula, but increased membrane GluR1 protein expression in the prefrontal cortex of WKY rats. These results suggest 2-week imipramine treatment significantly improves depressive behavior in WKY rats; however, the addition of ketamine in the first week fails to enhance the effect of imipramine. The underlying mechanisms of imipramine's anti-depressive effect may be associated with the down-regulation of βCaMKII and membrane GluR1 in the habenula, as well as the up-regulation of membrane GluR1 in the prefrontal cortex.


Subject(s)
Animals , Brain , Depression , Depressive Disorder , Disease Models, Animal , Down-Regulation , Imipramine , Ketamine , Male , Rats , Rats, Inbred WKY , Swimming , Up-Regulation
18.
Rev. panam. salud pública ; 38(6): 450-456, nov.-dic. 2015. ilus, tab
Article in Spanish | LILACS | ID: lil-788102

ABSTRACT

OBJETIVO:Investigar el patrón de distribución espacial de la tasa de homicidios y su relación con las características sociodemográficas en las delegaciones de Benito Juárez, Coyoacán y Cuauhtémoc de la Ciudad de México en el año 2010. MÉTODOS: Estudio inferencial de corte transversal que usa métodos de análisis espacial para estudiar la asociación espacial de la tasa de homicidios y las características demográficas. La asociación espacial fue determinada a través del cociente de localización, análisis de regresión múltiple y el uso de la regresión geográficamente ponderada. RESULTADOS: Los homicidios muestran un patrón de localización heterogéneo con altas tasas en zonas con uso del suelo no residencial, con baja densidad de población y baja marginación. CONCLUSIONES: El uso de herramientas de análisis espacial son instrumentos poderosos para el diseño de políticas de seguridad pública preventiva y recreativa que busquen reducir la mortalidad por causas externas como homicidios.


OBJECTIVE:Investigate the spatial distribution pattern of the homicide rate and its relation to sociodemographic features in the Benito Juárez, Coyoacán, and Cuauhtémoc districts of Mexico City in 2010. METHODS: Inferential cross-sectional study that uses spatial analysis methods to study the spatial association of the homicide rate and demographic features. Spatial association was determined through the location quotient, multiple regression analysis, and the use of geographically weighted regression. RESULTS: Homicides show a heterogeneous location pattern with high rates in areas with non-residential land use, low population density, and low marginalization. CONCLUSIONS: Spatial analysis tools are powerful instruments for the design of prevention- and recreation-focused public safety policies that aim to reduce mortality from external causes such as homicides.


Subject(s)
Animals , Cattle , Female , Humans , Male , Rats , Hypoxia/metabolism , Cation Transport Proteins/metabolism , Hypertension, Pulmonary/metabolism , Muscle, Smooth, Vascular/metabolism , Animals, Congenic , Hypoxia/genetics , Arterioles/metabolism , Cell Hypoxia , Cell Proliferation , Cells, Cultured , Chronic Disease , Cation Transport Proteins/deficiency , Cation Transport Proteins/genetics , Chromosomes, Mammalian/genetics , Gene Knockdown Techniques , Homeostasis , Hypertension, Pulmonary/genetics , Intracellular Space/metabolism , Muscle, Smooth, Vascular/cytology , Rats, Inbred WKY , Zinc/metabolism
19.
Rev. méd. Chile ; 143(1): 96-100, ene. 2015.
Article in Spanish | LILACS | ID: lil-742556

ABSTRACT

After years of discussion by the Chilean legislature, the Law Nº 20.584, which regulates health care related rights and duties of people, entered into force in Chile in October 2012. This bill represents an important step in the recognition and protection of health care related rights, welfare, dignity and duties of persons. It also intends to protect potential participants in clinical research. However such protective measures include explicit prohibitions such as the review of clinical records or the inclusion of people with mental or psychological handicaps as research participants. We herein discuss the implications of this law in medical research.


Subject(s)
Animals , Male , Rats , Gene Expression Regulation , MicroRNAs/genetics , MicroRNAs/metabolism , Disease Models, Animal , Glomerulonephritis/metabolism , Hypertension/pathology , Kidney Glomerulus/metabolism , Kidney Tubules/metabolism , Kidney/injuries , Kidney/metabolism , Rats, Inbred WKY , Time Factors , Transforming Growth Factor beta/metabolism , Ureter/pathology
20.
Rio de Janeiro; s.n; 2015. 71 f p.
Thesis in Portuguese | LILACS | ID: lil-756634

ABSTRACT

A hipertensão essencial humana, bem como a hipertensão desenvolvida em Ratos Espontaneamente Hipertensos (SHR), são caracterizadas pelo desenvolvimento de Pressão Arterial (PA) elevada na medida em que a idade avança, sem identificação da causa primária. Está bem estabelecido que este modelo animal apresenta estresse oxidativo (EOx) concomitante a hipertensão. O mecanismo pelo qual o antioxidante reduz a pressão não está claro, por essa razão, é necessário avaliar o comportamento destas enzimas envolvidas na homeostase da PA. Ratos Wistar-Kyoto (WKY) e SHR machos receberam ácido ascórbico, 200 mg / kg / dia por sonda orogástrica durante cinco semanas. A PA, a Hipertrofia Ventricular Esquerda (HVE), o Sistema Renina-Angiotensina (SRA), o Peptídeo Natriurético Atrial (ANP) e o EOx foram comparados entre os grupos por pletismografia, estereologia, microscopia confocal de varrimento a laser, microscopia eletrônica de transmissão, western blotting e análise do RT-qPCR. Os SHR tratados com ácido ascórbico reduziram a PA e a HVE. Além disso, as enzimas envolvidas na homeostase da PA, a renina e a Enzima Conversora de Angiotensina (ECA) normalizaram-se, bem como os Receptores tipo 1 de Angiotensina II (AT1). A grande quantidade de grânulos de ANP no grupo SHR foi reduzida pelo tratamento com ácido ascórbico. O balanço oxidativo foi restabelecido nos SHR tratados com este antioxidante. O EOx nos SHR eleva os níveis de renina e de PA. Estas espécies reativas de oxigênio podem ser envolvidas no mecanismo de sinalização para aumentar a expressão de ANP nos miócitos atriais. Estes dados também mostram que o tratamento com o antioxidante (vitamin C) reduz o EOx e normaliza a PA ao menos parcialmente pela redução de taxas de renina...


The essential hypertension, as well as the Spontaneously Hypertensive Rat (SHR), is characterized by the development of high BP (BP) with advancing age, with no identified primary cause. It is well established that this animal model presents OxS concomitant hypertension. The mechanism, by which the antioxidant reduces the pressure, is not clear, for this reason, it is necessary to evaluate the behavior of enzymes involved in the homeostasis of BP. Male Wistar-Kyoto (WKY) rats and SHR received ascorbic acid, 200 mg / kg / day by orogastric gavage with lasted five weeks. The BP, Left Ventricular Hypertrophy (LVH), renin-angiotensin system (RAS), Atrial Natriuretic Peptide (ANP) and OxS results have been extensively compared among groups by plethysmography, stereology, confocal laser scanning microscopy, transmission electron microscopy, western blotting and RT-qPCR analysis. The SHR treated with ascorbic acid reduced BP and LVH. Also, the enzymes involved in the homeostasis of BP, renin and Angiotensin Converting Enzyme (ACE) normalized, as well as Angiotensin II type 1 receptor (AT1R). The large amount of ANP granules in SHR group was reduced by treatment with ascorbic acid. Oxidative balance was reestablished in SHR treated with this antioxidant. OxS in SHR elevates renin levels and BP. These reactive oxygen species may be involved in the signaling mechanism for increased expression in ANP atrial myocytes. These data also show that treatment with antioxidant (vitamin C) reduces OxS and normalizes BP at least partly by reducing rates of renin...


Subject(s)
Animals , Rats , Hypertension , Blood Pressure/physiology , Renin-Angiotensin System , Antioxidants , Gene Expression , Microscopy, Confocal , Oxidative Stress , Blood Pressure , Rats, Inbred SHR , Rats, Inbred WKY , Renin
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