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background: Increased blood pressure variability is a novel risk factor for the development of target organ injury both in hyperten-sive and normotensive subjects, so its reduction should be considered as a new therapeutic goal. Objective: The aim of this study was to evaluate the effect of long-term oral carvedilol treatment on blood pressure, blood pressure variability and target organ injury in the left ventricle and thoracic aorta in a model of blood pressure liability. Methods: Twelve male Wistar rats submitted to sinoaortic denervation were treated during 8 weeks with a single dose of carvedilol 30 mg/kg or vehicle. At the end of treatment, echocardiographic evaluation and blood pressure and short-term variability measure-ments were performed. Left ventricular and thoracic aortic weights were determined and histological samples were prepared from both tissues. Metalloproteinase MMP-2 and transforming growth factor β (TGF-β) were quantified in the left ventricle and thoracic aorta. results: Carvedilol reduced systolic blood pressure and its variability in sinoaortic-denervated rats compared with the control group (126±5 vs. 142±11 mmHg, p<0.05; SD: 2.9±0.5 vs. 6.0±0.5 mmHg; p<0.05). A lower amount of connective tissue was found in carvedilol-treated animals. The expression of TGF-β decreased in both organs after carvedilol treatment. Conclusions: Chronic carvedilol treatment significantly reduces systolic blood pressure and its short-term variability in sinoaortic-denervated rats, decreasing the degree of left ventricular fibrosis.
introducción: El incremento en la variabilidad de la presión arterial resulta un nuevo factor de riesgo para el desarrollo de daño de órgano blanco en individuos tanto hipertensos como normotensos, por lo que se postula que su reducción debe considerarse una posible nueva meta terapéutica. Objetivos: Evaluar el efecto del tratamiento a largo plazo con carvedilol sobre la presión arterial, su variabilidad y el daño de órgano blanco en el ventrículo izquierdo y la aorta torácica en el modelo de la labilidad de presión. Material y métodos: Se incluyeron 12 ratas Wistar macho sometidas a desnervación sinoaórtica, las cuales fueron tratadas durante 8 semanas con una única administración diaria de carvedilol 30 mg/kg o vehículo. Finalizado el tratamiento se realizó la medición de la presión arterial y de la variabilidad a corto plazo y la evaluación ecocardiográfica. Se determinó el peso del ventrículo y de la aorta torácica y se realizaron preparados histológicos sobre ambos tejidos. Se cuantificó la expresión de metaloproteinasa 2 (MMP-2) y factor de crecimiento transformante β (TGF-β) en el ventrículo izquierdo y la aorta torácica. resultados: El carvedilol redujo la presión arterial sistólica y su variabilidad en las ratas con desnervación sinoaórtica en comparación con el grupo control (126 ± 5 vs. 142 ± 11 mm Hg, p < 0,05; DE: 2,9 ± 0,5 vs. 6,0 ± 0,5 mm Hg; p < 0,05). Se evidenció menor cantidad de tejido conectivo en los animales tratados con carvedilol. La expresión de TGF-β se encuentra disminuida en ambos órganos luego del tratamiento con carvedilol. Conclusiones: El tratamiento crónico con carvedilol reduce significativamente la presión arterial y su variabilidad a corto plazo en ratas con desnervación sinoaórtica, disminuyendo el grado de fibrosis del ventrículo izquierdo.
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There is no index or criterion of aortic barodenervation, nor can we differentiate among rats that have suffered chronic sham, aortic or sino-aortic denervation. The objective of this study was to develop a procedure to generate at least one quantitative, reproducible and validated index that precisely evaluates the extent of chronic arterial barodenervation performed in conscious rats. Data from 79 conscious male Wistar rats of about 65-70 days of age with diverse extents of chronic arterial barodenervation and used in previous experiments were reanalyzed. The mean arterial pressure (MAP) and the heart rate (HR) of all rats were measured systematically before (over 1 h) and after three consecutive iv bolus injections of phenylephrine (PHE) and sodium nitroprusside (SNP). Four expressions of the effectiveness of barodenervation (MAP lability, PHE ratio, SNP ratio, and SNP-PHE slope) were assessed with linear fixed models, three-level average variance, average separation among levels, outlier box plot analysis, and overlapping graphic analysis. The analysis indicated that a) neither MAP lability nor SNP-PHE slope was affected by the level of chronic sodium intake; b) even though the Box-Cox transformations of both MAP lability [transformed lability index (TLI)] and SNP-PHE slope [transformed general sensitivity index (TGSI), {((3-(ΔHRSNP-ΔHRPHE/ΔMAPSNP-ΔMAPPHE))-0.4-1)/-0.04597}] could be two promising indexes, TGSI proved to be the best index; c) TLI and TGSI were not freely interchangeable indexes for this purpose. TGSI ranges that permit differentiation between sham (10.09 to 11.46), aortic (8.40 to 9.94) and sino-aortic (7.68 to 8.24) barodenervated conscious rats were defined.
Subject(s)
Animals , Male , Rats , Aorta/innervation , Consciousness , Denervation/methods , Pressoreceptors/drug effects , Aorta/physiology , Blood Pressure/physiology , Heart Rate/physiology , Nitroprusside/pharmacology , Phenylephrine/pharmacology , Rats, WistarABSTRACT
Objective: To investigate the effect of arterial baroreflex (ABR) on survival rate of rats with cecal ligation and puncture (CLP)-induced sepsis. Methods: Male Sprague -Dawley rats were divided into 2 groups: sham-operated rats (n=22) and sinoaortic denervated (SAD) rats (n=22). Four weeks after SAD rats were subjected to CLP-induced sepsis, the blood pressure and heart period (HP) were monitored for 12 hours in conscious state and the survival of rats was observed. Results: Both the diastolic and systolic blood pressue gradually decreased after CLP; the HP shortened first and then drastically prolonged until the death of rats. At 12 h after CLP the survival rate of SAD rats was lower than that of the sham-operated rats (59% vs 86%). Significant differences were found between the Kaplan-Meier survival curves of the rats in 2 groups (P<0.05). Conclusion: ABR plays an important role in CLP-induced lethal sepsis model.
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The purpose of the present study was to determine the range of the influence of the baroreflex on blood pressure in chronic renal hypertensive rats. Supramaximal electrical stimulation of the aortic depressor nerve and section of the baroreceptor nerves (sinoaortic denervation) were used to obtain a global analysis of the baroreceptor-sympathetic reflex in normotensive control and in chronic (2 months) 1-kidney, 1-clip hypertensive rats. The fall in blood pressure produced by electrical baroreceptor stimulation was greater in renal hypertensive rats than in normotensive controls (right nerve: -47 ± 8 vs -23 ± 4 mmHg; left nerve: -51 ± 7 vs -30 ± 4 mmHg; and both right and left nerves: -50 ± 8 vs -30 ± 4 mmHg; P < 0.05). Furthermore, the increase in blood pressure level produced by baroreceptor denervation in chronic renal hypertensive rats was similar to that observed in control animals 2-5 h (control: 163 ± 5 vs 121 ± 1 mmHg; 1K-1C: 203 ± 7 vs 170 ± 5 mmHg; P < 0.05) and 24 h (control: 149 ± 3 vs 121 ± 1 mmHg; 1K-1C: 198 ± 8 vs 170 ± 5 mmHg; P < 0.05) after sinoaortic denervation. Taken together, these data indicate that the central and peripheral components of the baroreflex are acting efficiently at higher arterial pressure in renal hypertensive rats when the aortic nerve is maximally stimulated or the activity is abolished.
Subject(s)
Animals , Female , Male , Rats , Aorta/innervation , Baroreflex/physiology , Blood Pressure/physiology , Hypertension, Renal/physiopathology , Pressoreceptors/physiology , Autonomic Denervation , Chronic Disease , Electric Stimulation , Rats, WistarABSTRACT
OBJECTIVE: To study the reverse effect of angiotensin - converting enzyme (ACE) inhibitor - fosinopril on the structural changes of mesenteric resistance vessels in sinoaortic - denervated (SAD) rats. METHODS; The rats were randomly divided into SAD group, fosinopril treatment group after SAD operations; besides, another sham operation control group was established. The rats were put to death after medication and (or) feeding for 16 weeks. The histopathological changes of the second order branch of mesenteric artery taken from the rats were observed by light microscope and computer - assisted image analysis. RESULTS: The wall thickness, the ratio of wall thickness to internal diameter, the wall area, the ratio of numbers of smooth muscle cells to field of view of the mesenteric resistance vessels diminished significantly in the fosinopril treatment group; however, no significant change was noted for the relative area of the smooth muscle in this group vs. the SAD group. CONCLUSION: Fosinopril can efficiently inhibit the structural changes of mesenteric resistance vessels in SAD rats.
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BACKGROUND: There is substantial evidence that the vestibular system is involved in the regulation of blood pressure. Heart rate variability (HRV) is useful to investigate the role of the peripheral vestibular receptors and the baroreceptors in the orthostatic tolerance. METHODS: EKG was recorded during postural changes with the head up either after sinoaortic denervation or after bilateral labyrinthectomies in Sprague-Dawley rats. HRV, including mean, standard deviation, coefficient of variation (CV), and power spectrum, were analyzed from R-R intervals of EKG. RESULTS: Phenylephrine increased low frequency region and sodium nitroprusside increased high frequency region in the power spectral analysis of HRV in anesthetized rats. Postural changes decreased blood pressure transiently and then increased blood pressure gradually in control rats, but the depression of blood pressure induced by postural change was greater in rats with both sinoaortic denervation and bilateral labyrinthectomies. The increase of CV of HRV just after sinoaortic denervation or bilateral labyrinthectomies represents an unstable heart rate in resting position, however, CV of HRV was increased markedly by postural change 7 days after bilateral labyrinthectomies. Postural change with sinoaortic denervation increased low-frequency region representing sympathetic activity, whereas bilateral labyrinthectomies increased highfrequency region representing parasympathetic activity in power spectral analysis. CONCLUSIONS: These results suggest that both the peripheral vestibular receptors and the baroreceptors have subsidiary action in orthostatic tolerance and the peripheral vestibular receptors regulate blood pressure during postural change through the sympathetic nervous system.
Subject(s)
Animals , Rats , Blood Pressure , Denervation , Depression , Electrocardiography , Head , Heart Rate , Heart , Nitroprusside , Phenylephrine , Pressoreceptors , Rats, Sprague-Dawley , Sympathetic Nervous SystemABSTRACT
AIM: To study apoptosis and related genes expressions of cardiomyocytes in sinoaortic-denervated(SAD) rats. METHODS: SAD or sham-operation (Sham) was performed in male SD rats at the age of 10 weeks. After 16 weeks, apoptotic cells were stained in situ by terminal dexynucleotidyl-transferase mediated-dUTP nick end labeling (TUNEL). All stained results were analysised using computer image analysis techniques. Protein products and mRNA of Bcl-2, Bax, Fas and Fas-L were assessed by quantitative immunohistochemistry and RT-PCR. RESULTS: The numbers of apoptotic cardiomyocytes were significantly increased in SAD rats, the expressions of Bcl-2 were significantly decreased, whereas Bax,Fas and Fas-L were significantly increased in SAD rats. THZ]CONCLUSIONCONCLUSION: Apoptosis and dysregulation of gene expressions may be involved in the cardiomyocytes remodeling in SAD rats.
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Objective:To investigate the effect of arterial baroreflex(ABR)on survival rate of rats with cecal ligation and puncture(CLP)-induced sepsis.Methods:Male Sprague-Dawley rats were divided into 2 groups:sham-operated rats(n=22)and sinoaortic denervated(SAD)rats(n=22).Four weeks after SAD rats were subjected to CLP-induced sepsis,the blood pressure and heart period(HP)were monitored for 12 hours in conscious state and the survival of rats was observed.Results:Both the diastolic and systolic blood pressue gradually decreased after CLP;the HP shortened first and then drastically prolonged until the death of rats.At 12 h after CLP the survival rate of SAD rats was lower than that of the sham-operated rats(59% vs 86%).Significant differences were found between the Kaplan-Meier survival curves of the rats in 2 groups(P
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OBJECTIVE:To observe the effect of Xionggui dripping pills on sensitivity of baroreflex in selective sinoaortic denervated rats.METHODS:The dynamic blood pressures were monitored in selective sinoaortic denervated rats in waking stait,and the changes of baroreflex senitivity(BRS)were measured by modified SU Smyth method.RESULTS:Xionggui drip_ ping pill could improve BRS in sinus denervated rats.CONCLUSION:Since Xionggui dripping pill rectifies autonomic nerve function,it can protect target organs from damage in cardiovascular diseases.
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AIM To investigate the structural and functional remodeling of thoracic aortae in sinoaortic denervated (SAD) rats. METHODS SD rats underwent either SAD or sham operation at the age of 10 weeks. Sixteen weeks after operation, the contraction and relaxation of the thoracic aortae were measured in isolated preparations; The morphological changes of arteries were examined by using histopathological method and computer image analysis. RESULTS The NE induced contraction was increased and Ach induced relaxation of aortic rings was depressed in SAD rats; The structural remodeling of thoracic aortae was characterized by medial VSMC hypertrophy and matrix accumulations. CONCLUSION Vascular functional and structural remodeling can be found in sinoaortic denervated rats.
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The contents of ir-arg-vasopressin (ir-AVP) and ir-?-endorphin (ir-?-EP) in plasma, anterior pituitary (AP), posterior pituitary (PP), oblongata (OB) and hypothalamus (HP) were measured by radioimmunoassay after sinoaortic denervation (SAD) in rats. It was showed that the ir-AVP contents in OB and ir-?-EP contents in AP, PP and OB were significantly elevated 1 d after (SAD) (P
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Effects of anaesthesia and sinoaortic denervation (SAD) on the hypotensive action of , ketanserin were studied in rats. It was found that the dose-effect curves of kelanserin on blood pressure were the same between SAD and sham-operated rats under anaesthesia. However, in concious free ly moving rats, SAD sharpened the dose-effect curves. It is concluded that the lack of hypotensive effect of ketanserin in conscious normotensive animals is due in large part to the integrity of the arterial baroreflex.