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Abstract Background: Hypertensive condition can lead to abnormalities in heart structure and electrical activity. The electrocardiogram (ECG) is a recording of the electrical activity of the heart and widely used to diagnose and detect heart problem. Objective: We conducted a comparative ECG analysis between two hypertension models (L-NAME and SHR) and their controls (Wistar and Wistar-Kyoto) at six and 15 th week of age. Methods: Blood pressure was measured at the end of the 15 th week, and electrocardiography was performed at six and 15 weeks of age in anaesthetized rats. Data normality was confirmed by Kolmogorov-Smirnov test followed by unpaired Student's t-test and the Mann-Whitney for parametric and non-parametric data, respectively. Results are expressed as mean ± SD. The accepted level of significance was set at p < 0.05. Results: L-NAME exhibited prolongation of JT and QT intervals and SHR showed a decrease in heart rate when compared to Wistar-Kyoto and L-NAME. Wistar-Kyoto exhibited short PR interval with increased QRS complex, and only QT prolongation at 15 weeks compared to Wistar. Conclusions: All the hypertension models used in this study featured an increase in blood pressure. However, while SHR showed cardiac dysfunction, L-NAME exhibited changes in ventricular performance. These results may guide future studies on different types and models of hypertension.
Subject(s)
Animals , Male , Rats , Electrocardiography/methods , Hypertension/complications , Rats, Inbred WKY , Rats, Wistar , NG-Nitroarginine Methyl Ester/adverse effectsSubject(s)
Animals , Rats , Physical Conditioning, Animal , Body Temperature , Body Temperature Regulation , Physical ExertionABSTRACT
Objective This study aims to explore antihypertension and heart protective effect of acupuncture on SHR rats through the observation of blood pressure, cardiac ultrasound and pathology examination of SHR rats after needling the Zusanli (ST 36) and Taichong (LR 3). Methods A total of 14 SHR rats (10 weeks) were randomly divided into two groups:6 for model group and 8 for acupuncture group, another 6 SD rats (10 weeks) were used as the control group. SHR rats in the acupuncture group were fixed in the holder, and then they exposed both lower limbs for needling both sides Zusanli (ST 36) and Taichong (LR 3), and then they retained needles for 20 minutes per time with four weeks. The other two groups were fixed in the holder without needling. Blood pressure was examined each week. LVSs, LVDd, LVPWs, LVPWd were measured and recorded by cardiac ultrasound in the day after the whole course of acupuncture. LVM, LVMI, RWT were calculated. The hearts of rats were dissected and fixed in formalin for heart pathology detection after doing the cardiac ultrasound. Results After acupuncture treatment, compared with model group, the systolic blood pressure (SBP) of the third week (178.38 ± 9.47 mmHg vs. 190.00 ± 13.90 mmHg) and the fourth week (167.96 ± 23.47 mmHg vs. 195.47 ± 11.36 mmHg) of acupuncture group significantly decreased (P<0.01). The diastolic pressure (DBP) of the third week (139.33 ± 13.20 mmHg vs. 159.56 ± 12.89 mmHg) and the fourth week (132.92 ± 18.02 mmHg vs. 165.61 ± 13.36 mmHg) of acupuncture group significantly decreased (P<0.01). The LVSs (0.96 ± 0.07 vs. 1.28 ± 0.24), LVPWs (1.15 ± 0.08 vs. 1.68 ± 0.19) of the acupuncture group were significantly lower than those of the model group (P<0.01). The LVM (0.51 ± 0.12 vs. 0.84 ± 0.17) and LVMI (14.96 ± 1.53 vs. 23.65 ± 5.04) of acupuncture group were significantly lower than those of the model group (P<0.01). Histopathologic examination of the heart of the model group showed chronic inflammatory granulation tissue hyperplasia and fibrosis in myocardial outer membrane, but the acupuncture group showed no obvious changes in the heart tissue. Conclusions Acupuncture treatment on Zusanli (ST 36) and Taichong (LR 3) could effectively control the left ventricular hypertrophy by decreasing the SBP and DBP , prevent cardiac remodeling, and protect myocardial cells.
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Objective: To explore the effects of fosinopril on oxidative stress and vascular function in experimental rats with spontaneous hypertension. Methods: The rats were divided into 3 groups: Control group, with normal healthy rats (n=15), Spontaneous hypertension (SH) group (n=15), SH rats received intragastric administration of normal saline and Treatment group (n=15), SH rats received intragastric administration of fosinopril 10mg/(kg?d). All animals were treated for 7 weeks. Caudal artery systolic blood pressure (SBP) was measured at each week. blood levels of superoxide dismutase (SOD), reactive oxygen species (ROS), malonaldehyde (MDA) and NO2-/NO3- were determined in different groups respectively after 7 weeks. Moreover, thoracic aorta was taken to examine its diastolic reactive rate by acetylcholine (Ach)/sodium nitroprusside (SNP) induction. Results: From the 1st week until the end of experiment, compared with SH group, Treatment group had decreased SBP,P<0.05. With 7 weeks treatment, compared with Control group, SH group had decreased SOD activity, while increased protein levels of MDA and ROS, allP<0.05; compared with SH group, Treatment group showed elevated SOD activity (P=0.010), while reduced protein levels of MDA (P=0.021) and ROS (P=0.009). Compared with Control group, SH group had the lower content of NO2-/NO3-(P<0.001); both SH group and Treatment group had decreased diastolic rates by Ach/SNP induction,P<0.05. Compared with SH group, Treatment group presented the higher content of NO2-/NO3- and higher diastolic rate by Ach induction, allP<0.001. Conclusion: Fosinopril could improve vascular diastolic function via anti-oxidative stress in experimental SH rats, which might be one of its anti-hypertensive mechanisms.
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O TERPY promove efeito hipotensor de maior magnitude em ratos hipertensos (SHR e 2R-1C) do que em ratos normotensos (Wistar e 2R). Foi demonstrado anteriormente que o endotélio prejudica o efeito vasodilatador do TERPY em aorta de Wistar. No entanto, observamos que o endotélio melhora os efeitos vasodilatadores do TERPY em aorta de SHR. Vasos sanguíneos de menor calibre, tais como as artérias de resistência, estão associadas ao controle da resitência vascular periférica e da pressão arterial. Nossa hipótese é que o TERPY induz relaxamento nas artérias mesentéricas de resistência em SHR e que as células endoteliais modulam positivamente o efeito do TERPY nestes vasos sanguíneos. Portanto, o nosso objetivo foi avaliar o efeito vasodilatador do TERPY em anéis com e sem endotélio de artéria mesentérica de ratos SHR, o seu mecanismo de relaxamento e a participação da NOS sobre esse efeito. e a Nossos resultados mostraram que o TERPY induziu um efeito vasodilatador dependente da concentração em anéis de artérias mesentéricas (2º e 3º ramos) de SHR e de ratos Wistar. A potência do TERPY foi maior em anéis intactos do que em anéis sem endotélio em artérias mesentéricas de SHR, mas em Wistar o endotélio prejudicou o efeito do TERPY. Nas artérias mesentéricas sem endotélio de SHR, o efeito do TERPY é dependente da atividade da guanilato ciclase solúvel e de canais para potássio. Nas artérias mesentéricas intactas de SHR, o efeito de TERPY depende da atividade de eNOS, mas não é dependente das atividades de nNOS, iNOS ou da via da ciclooxigenase. O TERPY promove a fosforilação da eNOS nos resíduos de serina1177 e aumenta a concentração de óxido nítrico em células endoteliais isoladas de artérias mesentéricas de SHR. Nossos resultados mostraram que a guanilato ciclase solúvel, os canais para potássio e a eNOS estão envolvidos no efeito vasodilatador estimulado pelo TERPY nas artérias de resistência mesentérica de SHR. Numa segunda parte deste estudo, avaliamos o mecanismo de ação de TERPY e seu efeito sobre a atividade da eNOS em células endoteliais. As células HUVEC, WT-HEK e HEK-eNOS foram tratadas com TERPY em diferentes tempos (0 a 60 minutos). Foram analisados por Western blotting o efeito do TERPY sobre a fosforilação de eNOS, monômero e dímero da eNOS e sobre monômero e oligômero de caveolina-1. Também foi avaliado o efeito do TERPY na interação eNOS/Cav-1 através de co-imunoprecipitação. As alterações induzidas pelo TERPY sobre as concentrações de espécies reativas de oxigênio e peroxinitrito em células endoteliais foram medidas usando sonda DHE e biossensor 7-CBA, respectivamente. A concentração de óxido nítrico (NO) foi avaliada por sonda DAF-FM e sensor Cooper. O TERPY promoveu desacoplamento e disfunção da eNOS, dependente de BH4. A desestabilização dos oligômeros da caveolina-1 foi induzida pelo TERPY. Consequentemente, o TERPY reduziu a interação eNOS/Cav-1 e promoveu ativação da eNOS. Nossos resultados mostraram que a atividade da eNOS pode ser regulada de duas maneiras diferentes pelo TERPY. O TERPY promove desacoplamento e fosforilação da eNOS, promovendo uma estratégia diferente para a regulação da atividade desta enzima. As moléculas químicas ou biológicas como o TERPY que regulam a atividade da eNOS e aumentam a produção e a biodisponibilidade de NO teriam ações terapêuticas importantes para o tratamento de doenças vasculares associadas a hipertensão(AU)
TERPY promotes a hypotensive effect with greater magnitude in hypertensive rats (SHR and 2K-1C) than in normotensive rats (Wistar and 2K). Previously, it was demonstrated that endothelium impairs vasodilatory effect of TERPY in Wistar aorta. However, we observed that endothelium improves the vasodilatory effect of TERPY in SHR aorta. Smaller blood vessels, such as mesenteric arteries, are associated with the control of peripheral vascular resistance and blood pressure. We hypothesized that TERPY induces relaxation on mesenteric resistance arteries in SHR and endothelial cells modulate positively the TERPY's effect on these blood vessels. Therefore, our goal was to evaluate the vasodilator effect of TERPY in rings with and without endothelium of mesenteric arteries in SHR, the mechanism of relaxation and the participation of NOS on this effect. Our results show TERPY induced a concentration-dependent vasodilator effect in mesenteric arteries (2nd and 3 rd branches) rings from SHR and Wistar. The potency of TERPY was higher in intact than in denuded rings from SHR, but in Wistar, endothelium impair the TERPY's effect. In denuded mesenteric arteries from SHR, the relaxation effect induced by TERPY is dependent of soluble guanylate cyclase and activation of potassium channel. However, in intact mesenteric arteries from SHR, TERPY´s effect is modulated by eNOS activity, but it is not dependent of nNOS, iNOS or cyclooxygenase pathway activities. TERPY promotes eNOS3 Ser1177 phosphorylation and increases nitric oxide concentration in isolated endothelial cells of mesenteric arteries from SHR. Together, our results showed that soluble guanylate cyclase, potassium channels, and eNOS are involved in the vasodilator effect of TERPY in mesenteric resistance arteries from SHR. In a second part of this study, we aimed to evaluate the mechanism of action of TERPY and its effect on eNOS activity in endothelial cells. HUVEC, WT-HEK and HEK-eNOS cells were treated with TERPY at different times (0 to 60 minutes). Were analyzed by western blotting the TERPY`s effect on eNOS monomer, dimer and phosphorylation and on monomer and oligomer of caveolin-1. It was also evaluated the effect of TERPY in the interaction between eNOS/Cav-1 through co-immunoprecipitation. Alterations induced by TERPY on reactive oxygen species and peroxynitrite concentrations in endothelial cells were measured by using DHE probe and biosensor 7-CBA, respectively. Nitric oxide fluorescence was assessed by DAF-FM probe and Cooper sensor. TERPY promoted eNOS uncoupling and eNOS dysfunction, which is BH4-dependent. Caveolin-1 oligomers destabilization was induced by TERPY. Consequently, TERPY reduced eNOS/Cav-1 interaction and promoted eNOS activation. Our results show that eNOS activity can be regulated in two different ways by TERPY, leading to eNOS uncoupling and leading to eNOS phosphorylation, promoting a strategy for eNOS regulation. Chemical or biological molecules as TERPY that regulates eNOS activity and increase NO production and bioavailability are potential therapeutic drugs for the treatment of vascular diseases associated with hypertension(AU)
Subject(s)
Animals , Rats , Nitric Oxide , Nitric Oxide Synthase Type III , Rats, Inbred SHR , Vasodilation , Caveolin 1 , Endothelium, Vascular , Hypertension , Mesenteric Arteries , Vascular DiseasesABSTRACT
PURPOSE: To evaluate the effect of exercise (swimming) on pregnancy in spontaneously hypertensive rats (SHR). METHODS: Thirty three pregnant female SHR were distributed into three groups (n=11 animals/group): SHR Control=non-exercised (sedentary); SHR Ex0 = exercised from day zero to day 20 of pregnancy; and SHR Ex7 = exercised from day 7 to 20 of pregnancy. Body weight and systolic blood pressure were indirectly measured during pregnancy. On gestational day 21, the rats were anaesthetized and uterine content was withdrawn for analysis of maternal reproductive outcome parameters and fetal development. RESULTS: The reduced blood pressure percentage was higher in SHR Ex0 and SHR Ex7 compared to SHR Control group. Weight gain was present in all pregnancy periods, but it was lower in SHR Ex7 than in SHR Control dams. The exercise increased the pre-implantation loss rate. The post-implantation loss rate was lower in SHR Ex0 group. SHR Ex7 group showed a significantly higher percentage of fetuses classified as small for gestational age as compared to others groups. CONCLUSION: The exercise contributed to lowering gestational blood pressure in SHR rats, but had a negative impact on the developing embryo. .
Subject(s)
Animals , Female , Male , Pregnancy Outcome , Physical Conditioning, Animal/physiology , Pregnancy/physiology , Blood Pressure/physiology , Body Weight/physiology , Eating/physiology , Fetal Development/physiology , Rats, Inbred SHR , Swimming/physiology , Time Factors , Weight Gain/physiologyABSTRACT
Introdução: Ainda é controverso se ocorre sinergismo entre as diferentes medidas não farmacológicas utilizadas no tratamento da hipertensão arterial. Objetivo: Avaliar o efeito do exercício físico aeróbico, da sobrecarga oral de potássio e da sua associação sobre a pressão arterial, metabolismo glicídico, excreção urinária de albumina e morfologia glomerular de ratos espontaneamente hipertensos (SHR). Métodos: SHRs foram divididos em: Grupo Controle (SHR; dieta padrão e sedentário, n = 10); Grupo Exercício (SHR + E; treinado em esteira rolante, dieta padrão, n = 10), Grupo Potássio (SHR + K; sedentário, dieta rica em potássio, n = 10) e Grupo Exercício + Potássio (SHR + E + K; exercitado, dieta rica em potássio, n = 10). Semanalmente, foi aferido o peso corporal (PC) e a pressão arterial de cauda (PAC). Ao final de 16 semanas, foi realizado o Teste de Tolerância oral a Glicose. A albuminúria foi determinada nos períodos basal, na 8ª e 16ª semana. Após o sacrifício, foi realizada a análise do índice de esclerose glomerular e a pesagem da gordura visceral. Resultados: A PAC e o PC não variaram significativamente. Houve melhora da sensibilidade à insulina no Grupo Exercício e Grupo Potássio, mas não no Grupo Exercício + Potássio. Na 16ª semana, a albuminúria de todos os grupos foi significativamente menor que o grupo SHR Controle. O índice de esclerose glomerular e o peso da gordura visceral também foram significativamente menores em todos os grupos tratados quando comparados ao controle. Conclusão: A dieta rica em potássio e o exercício físico determinaram melhora no metabolismo glicídico, na albuminúria e na morfologia glomerular, porém, a sobreposição ...
Introduction: It is still controversial whether there are synergistic effects among different non-pharmacological interventions used in the treatment of hypertension. Objetives: To evaluate the effect of aerobic exercise, oral supplementation of potassium and their combination on blood pressure, glucose metabolism, urinary albumin excretion and glomerular morphology in spontaneously hypertensive rats (SHR). Methods: SHR were divided into groups: Control Group (SHR; standard diet and sedentary, n = 10), Exercise Group (SHR + E; trained on a treadmill, standard diet, n = 10), Potassium Group (SHR + K; sedentary, potassium supplementation, n = 10) and Group Exercise + Potassium (SHR + E + K, exercise, potassium supplementation n = 10). Weekly, body weight (BW) and tail blood pressure (TAP) were measured. At the end of 16 weeks, a Oral Glucose Tolerance Test was performed. Albuminuria was determined in the baseline period, at 8th and at 16th week. After sacrifice, the analysis of glomerular sclerosis index and visceral fat weight was performed. Results: The TAP and BW did not change significantly. There was improvement in insulin sensitivity in SHR + E and SHR + K, but not in SHR + E + K. At week 16, albuminuria in all groups was significantly lower than the SHR control. The glomerular sclerosis index and visceral fat content were also significantly lower in all groups compared to control. Conclusion: An oral supplementation of potassium and exercise led to an improvement in glucose metabolism, in albuminuria and glomerular morphology, however, the overlap of the treatments did not show synergism. .
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Animals , Male , Rats , Albuminuria/metabolism , Albuminuria/physiopathology , Blood Pressure/physiology , Glucose/metabolism , Hypertension/metabolism , Hypertension/physiopathology , Physical Conditioning, Animal/physiology , Potassium/administration & dosage , Dietary Supplements , Rats, Inbred SHRABSTRACT
Objective To investigate the protective effect of antihypertensive drug NO.1 on brain cortical tissue in spontaneously hypertensive rats.Methods A total of 60 spontaneously hypertensive rats (SHR,30 males and 30 females) and 12 healthy Wistar rats (6 males and 6 females) weighed (200 20) g,were randomly divided into 6 groups.Model group (SHR,n=12) and control group (healthy Wistar rats,n=12) were given the same dose of placebo.Captopril group (SHR,n=12) were given captopril 5 mg · kg-1 · d-1.The low-,median-and high-dose groups of antihypertensive drug NO.1 were given 0.25,0.5 and 1 g · kg 1 · d-1 respectively.After 4 weeks of treatment,carotid artery blood pressure was detected.All rats were sacrificed,and brain tissue samples were taken.The expressions of Bcl-2,Bax,necrosis factor NF-κB P65,chloride channel 2 and 3 (CLC-2 and CLC-3) were determined by RT-PCR and Western blotting.Results After 4 weeks of antihypertensive NO.1 treatment,SHR carotid artery blood pressure was (182.8 ± 7.3)mmHg in low dose group,(170.3±9.4) mmHg in medium dose group,and (163.9±10.6) mmHg in high dose group; and (205.4 ± 11.3)mmHg in the model group.Antihypertensive drug NO.1 significantly reduced blood pressure in spontaneously hypertensive rats,and had a concentrationresponse relationship (P＜0.05).Antihypertensive drug NO.1 decreased the expressions of Bax,CLC-2 and CLC-3,and increased the expressions of Bcl-2 and NF-κB P65.Conclusions Antihypertensive drug NO.1 plays a protective role in hypertension-induced cell injury by changing the metabolic enhancement in hypertension-induced cell volume decrease.
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BACKGROUND:Proto-oncogene c-Src plays an important role in regulating cardiovascular diseases such as hypertension. At present, there were no studies concerning exercise intervention effects on c-Src expression in aortic endothelial cels so as to regulate hypertension. OBJECTIVE: To observe the effects of aerobic exercise on c-Src mRNA expression and c-Src activity in the aorta blood vessel endothelial cels of spontaneous hypertensive rats. METHODS: A total of 8 male Wistar rats were considered as normal control group. Sixteen spontaneous hypertensive rats were randomly assigned to 8 rats as spontaneous hypertension group and 8 rats as spontaneous hypertension exercise group. Rats in the spontaneous hypertension exercise group carried on 90 minutes unloaded aerobic swimming every day, 6 days a week, for 8 weeks. The rats in the normal control group and spontaneous hypertension group did not swim. Blood pressure of rats was measured once a week. 8 weeks later, the c-Src mRNA expression and c-Src activity were determined in aortic vascular endothelial cels of rats in each group. RESULTS AND CONCLUSION: Compared with spontaneous hypertension group, blood pressure was lower, but c-Src mRNA expression and c-Src activity were significantly higher in the spontaneous hypertension exercise group. The c-Src activity and c-Src mRNA expression were higher in the spontaneous hypertension exercise group than normal control group and spontaneous hypertension group (P < 0.01). Results indicated that aerobic exercise can promote the increase in c-Src activity and c-Src mRNA expression in aortic endothelial cels of spontaneous hypertensive rats.
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Objective:To explore influence of monotherapy or combined use of telmisartan and pyridoxamine on aor-tic remodeling in spontaneously hypertensive rats (SHR)and its possible mechanism.Methods:A total of 48 male SHE were randomly and equally divided into hypertension control group,telmisartan group,group,and telmisartan+ group (combined treatment group). Kyoto Wistar rats of the same age and gender were regarded as normal blood pressure control group (normal control group). Thoracic aortic section were examined by related staining af-ter 16 weeks intervention to calculate the ratio of aortic wall thickness to radius of lumen (Tw/Rl),the ratio of wall area to lumen area (W/L),and the area ratio of media elastic fiber/collagen fiber. Concentrations of related en-zymes and receptor etc. of abdominal aortic were measured.Results:Compared with hypertension control group, there was significant rise in ratio of media elastic fiber/collagen fiber area and significant reduction in media collagen fiber/media area ratio in telmisartan group,pyridoxamine monotherapy group and combined treatment group,and there were significant decrease in Tw/Rl [(0.17±0.02)vs. (0.12±0.01)]and W/L [(0.29±0.03)vs. (0.22± 0.02)]ratios in combined treatment group,P <0.05 or <0.01;immunohistochemistry indicated that there were significant reductions in thoracic aortic receptor of advanced glycation end products (RAGE) [(0.24±0.03)vs.(0.17±0.03)]and extracellular signal-regulated kinase 1/2 (p-ERK1/2 )expression [(0.63 ± 0.06)vs. (0.37± 0.04)]in combined treatment group,P <0.05,<0.01. Fluorescence quantitative PCR indicated that medication can significantly reduce nicotinamide adenine dinucleotide phosphate (NADPH)oxidase subunit p47phox mRNA ex-pression (P <0.01 all),especially in combined treatment group (P =0.001).Conclusion:Combined use of telmis-artan and pyridoxamine is superior to the single use of either drug on improving thoracic aortic remodeling in SHR, the mechanism may be related to it reduces local expression of RAGE and p-ERK1/2 ,and inhibits oxidase subunit p47 of NADPH.
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Objective To investigate the effects of the exercise training on the cognitive function ,choline acetyltransferase (ChAT) activity and acetylcholinesterase (AchE) activity in stroke prone spontaneously hypertensive rat (SHR/SP) vascular de-mentia model .Methods 30 male SHR/SP rats were randomly divided into sham operation group ,model group and exercise group (n=10) .The VD model was established by the fractional ligation of bilateral carotid artery (2-VO) .The sham operation group and the model group were given the normal feeding without intervention after operation ;the exercise group adopted the treadmill exer-cise(DSPT-1) for 8 weeks .After the exercise ,the Morris maze test was conducted for evaluating the cognitive function in each group .The rats were finally killed for detecting the ChAT activity and AchE activity of hippocampus .Results In the positioning navigation training ,the latency period of the sham operation group was significantly short than that of the exercise group and the model group ,but the latency period of the exercise group was obviously short than that of rats in the model group (P<0 .05);in the spatial exploration test ,the rats in the sham operation group had more frequency of crossing platform than the other two groups ,the exercise group had more frequency of crossing platform in platform quadrant than the model group (P<0 .05);the exercise training could increase the ChAT activity and lower the AchE activity of hippocampus .Conclusion The exercise training can improve the function of hippocampal cholinergic system in SHR/SP and then increase the cognitive ability .
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Few articles have shown changes in bone metabolism caused by hypertension. The objective of this study was to investigate the relationship between hypertension and bone healing. Circular critical-size defects 5 mm and 2 mm in diameter were created, respectively, on the left and right side of the mandible in 40 spontaneously hypertensive and 40 control Wistar-Kyoto rats. Five animals from each strain were killed 2, 3, 5, 10, 15, 30, 60 and 90 days after surgery. The macroscopic evaluation showed great mandibular angle deformation on the left side and non-healed defects on both sides and groups. Histological evaluation revealed similar bone healing on both sides, with initial necrosis in the central area, and fibrosis and angiogenesis within the first 5 days. From the 10th postoperative day on, the newly formed bone displayed progressive thickening until the 90th postoperative day, when the defect margins presented a compact bone structure. Furthermore, the statistical analysis of the histometric data did not reveal any significant hypertension effect on bone healing in the defect area. These results suggest that bone healing was not different between spontaneously hypertensive rats and control rats.
Subject(s)
Animals , Male , Rats , Bone Regeneration/physiology , Hypertension/metabolism , Mandibular Injuries/metabolism , Wound Healing/physiology , Mandible/metabolism , Mandible/surgery , Mandibular Injuries/pathology , Mandibular Injuries/surgery , Postoperative Period , Rats, Inbred SHR , Rats, Inbred WKY , Rats, Wistar , Time FactorsABSTRACT
PURPOSE: Evaluation of colonic healing in spontaneously hypertensive rats. METHODS: Fifty male, young and inbred rats were used. Twenty-five Wistar Kyoto rats (WKY) as control and twenty-five spontaneously hypertensive rats (SHR) as an experimental group. Colotomy and bowel suture at 2.5 cm from the peritoneal reflection were performed. All animals were allocated randomly into sub-groups for review at the third, seventh and fourteenth days after surgery. We evaluated the concentration of angiotensin II, the burst pressure, epithelialization, the organization of the tunics of the bowel wall, inflammatory response and collagen deposition. RESULTS: The burst pressure, epithelialization, organization of the tunics and collagen deposition was not significant between groups. The inflammatory reaction was more intense in the control group on the third postoperative day (p=0.023) as the experimental group on the remaining time. CONCLUSION: Systemic arterial hypertension in rats did not influence significantly the healing process of colonic anastomoses.
OBJETIVO: Avaliar a cicatrização colônica em ratos espontaneamente hipertensos. MÉTODOS: Cinquenta ratos machos, jovens e isogênicos. Vinte e cinco ratos da linhagem Wistar Kyoto (WKY) como controle e vinte e cinco ratos espontaneamente hipertensos (SHR) como grupo experimento. Realizou-se colotomia e colorrafia a 2,5 cm da reflexão peritoneal. Alocaram-se os animais aleatoriamente em sub-grupos para avaliação no terceiro, sétimo e décimo quarto dias de pós-operatório. Foram avaliados a concentração de angiotensina II, a resistência da anastomose à insuflação, a epitelização, a organização das túnicas da parede intestinal, a reação inflamatória e a deposição de colágeno. RESULTADOS: A avaliação da resistência da anastomose, epitelização, organização das túnicas e deposição de colágeno não foi significativa entre os grupos. A reação inflamatória foi mais intensa no grupo controle na avaliação do terceiro dia de pós-operatório (p=0,023) igualando-se ao grupo experimento nos demais tempos. CONCLUSÃO: A hipertensão arterial sistêmica, em ratos, não influenciou de forma significante no processo cicatricial de anastomoses do cólon.
Subject(s)
Animals , Male , Rats , Colon/surgery , Hypertension/physiopathology , Wound Healing/physiology , Anastomosis, Surgical , Angiotensin II/analysis , Blood Pressure/physiology , Collagen/metabolism , Colon/pathology , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Postoperative Period , Random Allocation , Rats, Inbred SHR , Rats, Inbred WKY , Surgical Wound Dehiscence/physiopathology , Time FactorsABSTRACT
Objective: To explore influence of exercise training and angiotensin-converting enzyme inhibitor (perindopril) on blood pressure, aortic compliance and cardiovascular tissue structure in spontaneously hypertensive rats (SHR). Methods: A total of 38 SHR aged seven weeks were divided into control group (C group, n=9), exercise group (Exe group, n=9), perindopril group (Per group, n=10) and perindopril + exercise group (Per＋Exe group, n=10). SHRs were observed for eight weeks, and tail-cuff method was used to measure systolic blood pressure（SBP）once a week. When rats were 15 weeks old, regression line（once linear function）was obtained by single regression analyzing the relation between blood pressure and pulse wave velocity（PWV）. The b of this once linear function was used as index of aortic compliance（there was negative relationship between b and aortic compliance）. The left ventricular mass （LVM）/body weight（BW）was used to evaluate ventricular thickening, and aortic weight （AO）/ BW was regard as index of vascular thickening. Results: Compared with C group, SBP of Exe group significantly decreased on 12 weeks old (P0.05）. On 15 weeks old, the LVM/BW [(2.19±0.36) mg/g, (2.16±0.32) mg/g ] and AO/BW [(0.20±0.01) mg/g, (0.19±0.01) mg/g] of Per group and Per+ Exe group significantly decreased compared with C group [(2.95±0.58) mg/g, (0.26±0.01) mg/g], P<0.05 all, but there was no significant difference in these indexes between Per group and Per+ Exe group and between C group and Exe group（P＞0.05 both）. The b （index of aortic compliance）were [（C group ：（21.2±1.2）, Exe group：（20.5±1.4）, Per group：（14.8±1.6），Per＋Exe group：（15.0±1.3）] respectively, there was no significant difference between Per group and Per+ Exe group and between C group and Exe group（P＞0.05 both）. Conclusion: The exercise training of eight weeks possesses certain lowering blood pressure tendency, but no significant influence yet for aortic compliance and cardiovascular tissue structure in spontaneously hypertensive rats.
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INTRODUÇÃO: A elevação do índice de massa corporaleapresençadesíndromemetabólica se associam com diminuição da função renal e o aparecimento de doença renal terminal. OBJETIVO: Avaliar o efeito da sobreposição de um modelo de obesidade experimental e hipertensão arterial sobre a pressão arterial, peso corporal e parâmetros metabólicos e renais de ratos. MÉTODOS: Foram estudados ratos machos das cepas Wistar e espontaneamente hipertensos (SHR). Os grupos MSG receberam glutamato monossódico no período neonatal (WST + MSG e SHR + MSG). Os animais controles receberam salina no período neonatal (WST e SHR). Após completarem três meses de vida, por 12 semanas foram pesados e tiveram a pressão arterial de cauda aferida semanalmente. A determinação de microalbuminúria foi realizada nas semanas 0, 4, 8 e 12. Ao final do período de acompanhamento, coletou-se sangue para glicemia de jejum, creatinina e perfil lipídico. Os rins foram retirados, corados e o índice de esclerose glomerular foi calculado. RESULTADOS: A administração de MSG produziu maior ganho percentual de peso corporal, elevação da glicemia de jejum e maior grau de lesão glomerular nos ratos WST -MSG e SHR -MSG quando comparados aos seus controles. Houve maior excreção urinária de albumina nos ratos do Grupo SHR + MSG quando comparados aos SHR. Não houve diferença estatística na pressão arterial de cauda, creatinina e parâmetros do metabolismo lipídico. CONCLUSÕES: A associação de obesidade neuroendócrina e a hipertensão arterial promoveram alterações morfológicas e funcionais no glomérulo mais severas do que aquelas observadas nos ratos somente hipertensos.
INTRODUCTION: Increased body mass index and the metabolic syndrome are associated with decreased renal function and the development of end-stage kidney disease. OBJECTIVE: To evaluate the effect of the overlap between an experimental model of obesity and genetic hypertension on the blood pressure, body weight and metabolic and kidney parameters of rats. METHODS: We studied male rats of the Wistar (WST) and spontaneously hypertensive rats (SHR) strains. Monosodium glutamate (MSG) was administered in the neonatal period to both strains, to make up two groups: WST + MSG and SHR + MSG. Animals in the control groups (WST and SHR) received saline. After completing three months of life, a 12-week follow-up period ensued, during which bi-weekly measurements of body weight (BW) and tail-cuff blood pressure (TCBP) were obtained. Microalbuminuria was analyzed at weeks 0, 4, 8 and 12. At the end of the follow-up period, blood was obtained for fasting glucose, plasma creatinine, and lipid profile determinations. The kidneys were removed, stained, and the glomerular sclerosis index was calculated. RESULTS: The administration of MSG produced higher percentage body weight gain, higher fasting blood glucose and a higher degree of glomerular injury in WST-MSG and MSG-SHR rats, compared to their controls. Greater urinary albumin excretion was observed in SHR + MSG rats, when compared to SHR. There was no statistical difference in the TCBP, creatinine, and lipid profile. CONCLUSIONS: The association of neuroendocrine obesity and arterial hypertension promoted morphological and functional changes in the glomerulus. These changes were more severe than those observed in hypertensive-only rats.
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Animals , Male , Rats , Blood Pressure , Body Weight , Disease Models, Animal , Hypertension/metabolism , Hypertension/physiopathology , Kidney/physiopathology , Obesity/metabolism , Obesity/physiopathology , Neurosecretory Systems , Rats, Inbred SHR , Rats, WistarABSTRACT
BACKGROUND: Hypertensive myocardial fibrosis promotes abnormalities of cardiac function that may adversely affect the clinical outcome of hypertensive patients. Imatinib mesylate blocks receptor tyrosine kinase and is clinically used to treat leukemia. Platelet-derived growth factor (PDGF) is a downstream target of receptor tyrosine kinases. Cardiac fibroblasts can be activated by PDGF. Thus we evaluated whether imatinib attenuate myocardial fibrosis and prevents diastolic dysfunction in spontaneously hypertensive rats (SHR). METHODS: 8 weeks old male SHRs were subjected to treatment with 8 weeks of low dose imatinib (SHR-10; 10 mg/kg), high dose imatinib (SHR-30; 30 mg/kg) or saline (SHR-C; n = 6 in each group). At the age of 16 weeks, all rats underwent hemodynamic studies and Doppler echocardiography, and were sacrificed. Their hearts were extracted for histopathological, immunoblotting and quantitative reverse transcriptase-polymerase chain reaction analyses. RESULTS: While imatinib did not affect blood pressure (BP), it markedly reduced perivascular and interstitial fibrosis in the hearts of SHR. Echocardigram showed that high-dose imatinib significantly reduced left ventricular (LV) wall thickness (septal/posterior wall; SHR-C vs. SHR-30: 18 +/- 2/19 +/- 2 mm vs. 15 +/- 1/14 +/- 1 mm; p < 0.05) and improved the parameters of LV diastolic function such as E/A ratio (SHR-C vs. SHR-30: 1.60 +/- 0.10 vs. 1.86 +/- 0.20; p < 0.05). Imatinib also significantly reduced mRNA expression of collagen III and PDGF beta-receptor tyrosine phosphorylation in the hearts of SHR. CONCLUSIONS: These results suggest that imatinib, especially high dose, could attenuate myocardial fibrosis and prevent LV diastolic dysfunction in hypertensive rat model by decreased activity of PDGF. Imatinib may provide a potential therapeutic approach for hypertensive heart disease.
Subject(s)
Animals , Humans , Male , Rats , Benzamides , Blood Pressure , Collagen , Diastole , Echocardiography , Echocardiography, Doppler , Fibroblasts , Fibrosis , Heart , Heart Diseases , Hemodynamics , Immunoblotting , Leukemia , Mesylates , Phosphorylation , Phosphotransferases , Piperazines , Platelet-Derived Growth Factor , Protein-Tyrosine Kinases , Pyrimidines , Rats, Inbred SHR , RNA, Messenger , Tyrosine , Imatinib MesylateABSTRACT
Objective To investigate the effect and mechanism of ganoderma acid in therapy of the rat essential hypertension.Methods 30 male spontaneously hypertensive rat (SHR) were divided randomly into three groups:control group (CG),ganoderma acid group (Gan) and captoril (Cap) as positive control group.SHR were fed with distilled water (10 ml/kg) in control group,ganoderma acid (0.6 g/kg ) in Gan group,catopril (0.03 g/kg) in Cap group.After 8-weeks therapy,5 ml blood was extracted,rats in every group were sacrificed to get the aorta.The mRNA expression of superoxide dismutase (SOD),nitric oxide synthase (NOS) and high density lipoprotein (HDL) were detected by RT-PCR and the apoptosis of endothelial cells were measured by flowcytometry.Results After the 8 weeks therapy,as compared with the CG group,blood pressure of SHR in Gan group became stable[(112.6±3.2) mm Hg](P＜0.01).The expression of SOD,NOS and HDL showed obviously upregulated,and apoptosis of endothelial cell decreased significantly (P＜0.01).NO contents increased,and MDA,ET-1 decreased (P＜0.01).The contents of LDL decreased and HDL increased (P＜0.01).Conclusions Ganoderma acid may improve the function of endothelial cell and decrease the blood pressure by promoting the mRNA expression and activity of SOD,cleaning the radical ions and inhibiting the apoptosis of the endothelial cell.
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Objective To develop a model of type 2 diabetes with early renal injury on spontaneously hypertensive rats (SHR). Methods The 6-week old SHR were fed with the diets enriched with sucrose (20%, W/W), lard (10%, W/W), cholesterol (2.5%, W/W) and chleolate (1%, W/W) to induce insulin resistance. Hyperglycemia was developed by intraperitoneal injection of streptozotocin (STZ, 35 mg/kg). Wistar-Kyoto rats (WKY) were used as normal controls. Rats with plasma glucose (PGL) ≥ 16.7 mmol/L were diagnosed as diabetes. Eight weeks after the induction of diabetes, plasma triglyceride (TG), cholesterol (CHO), glucose, systolic pressure(SP), 24-h urine protein excretion (Upro) were examined in all the rats, and the homeostasis model assessment of insulin resistance (HOMA-IR) was analyzed. Renal pathological changes were studied by immunohistochemical staining and electron microscope. Results After 2 weeks on the high sucrose and fat diets, the model rats exhibited significant increase in basal PGL, TG and CHO levels as compared to control rats (P<0.05, respectively). The insulin resistance was developed in model rats demonstrated by the higher HOMA-IR (5.03±0.38 vs 2.61±0.34, P<0.05). At the end of the experiment, model rats were associated with hypertension. Upro level was significantly increased in model rats compared with that in controls [(57.58±16.54) mg/24 h vs (5.35±1.90) mg/24 h, P<0.01]. The kidney hypertrophy index (KWI) was significantly increased in the model rats compared to controls (P <0.05). Moreover, the diabetic model rats showed glomerular hypertrophy, foot process effacement, micro villous transformation, glomerular basement membrane (GBM) thickening. Conclusion A rat model is successfully established, which presents typical features of human type 2 diabetes and can be served as an ideal model to study the diabetic nephropathy.
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Objective To investigate the molecular basis for anti-ventricular arrhythmic effects by losartan through measuring alteration in mRNA and protein levels of key K+ α channel-and-β subunits (Kv4.2,Kv4.3 and KChIP2) in ventricular myocytes in spontaneously hypertensive rats (SHRs).Methods SHRs were randomly assigned to losartan[10mg·kg-1·d-1,n=12] or placebo (n= 12) with age-and weight-matched WKY rats (n = 12) as control.After 8 weeks of treatment,cardiomyocytes were isolated by enzymolysis.Action potential of cardiomyocytes Ito was recorded,mRNA and protein levels of Kv4.2,Kv4.3 and KChIP2 were assessed by reverse transcriptase polymerase chain reaction and Western blot.Results The action potential duration (APD) measured at 50% and 90% repolarization was shorter in losartan group [(16.82 ± 3.79) ms and (68.49±13.25) ms] than in SHR control group [(24.56±4.59) ms and (73.26±15.47) ms,all P<0.01].Losartan increased Ito current density associated with significant increases in the mean levels of mRNA and protein of Kv4.2 and Ky4.3,and with significant decreases in the mean levels of mRNA and protein of KChIP2 compared with those in placebo SHR (all P<0.01).Conclusions Chronic blockade of AT1 receptors with losartan reverses cardiomyocytes electrical remodeling in SHR,resulting in the shortening of APD,which is associated with increasing Ito density by increasing mRNA and protein expression of Kv4.2,Kv4.3 and by decreasing mRNA and protein expression of KChIP2.
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Objective To observe the Klotho expression in kidneys and renal tubular epithelial cells apoptosis in spontaneously hypertensive rats (SHRs) and the effects of cordyceps sinensis (CS), in order to study the mechanism of protective effects of CS on renal tubular cells apoptosis in hypertensive renal damage. Methods Twenty 22-week-old male SHRs were control group. After 8 weeks, the levels of 24 hours urinary protein (Upre), urinary N-acetyl-β-D-glucosaminidase (NAG), serum creatinine (Scr), blood urea nitrogen (BUN) and renal pathological changes were detected; the mRNA expression of Klotho, 053 and 021 was detected by RT-PCR; the protein expression of Klotho, 053, 021 and cleaved-caspase-3 was tested by Western blotting. TUNEL assay was applied to evaluate the renal tubular cell apoptosis. Results As compared to SHR group, the levels of 24 h urinary protein content [(52.16±29.3) mg, (49.97±32.5) mg, (54.67±30.09) mg vs (96.52±36.94) mg], urinary NAG [(44.13±9.11), (42.75±8.33), (41.96±7.88) U/L vs (54.07±6.57) U/L], Sct [(45.25±9.55), (43.76±8.65), (45.18±7.28) μmol/L vs (53.84±10.21) μmol/L]and BUN [(8.25±1.03), (8.40±1.58), (8.32±0.98) mmol/L vs (8.91±1.24) mmol/L]were decreased (all P<0.05), renal pathological changes were relieved, the levels of Klotho expression were up-regulated and the levels of p53 and p21 expression and cleaved-caspase-3 protein expression were down-regulated (all P<0.01), tubular cell apoptosis was decreased [7.56%±0.52%, 7.93%±0.37%, 7.37%±0.36% vs 13.32%±0.64%, P<0.01] in CS, Los and CS+Los group. Conclusions Klotho, p53 and p21 play important roles in renal tubular cells apoptosis in hypertensive renal damage. CS can up-regulate Klotho expression, down-regulate p53 and p21 expression and decrease the cleaved-caspase-3 expression and tubular cell apoptosis to ameliorate the hypertensive renal damage.