Effects of Chronic Carvedilol Administration on Blood Pressure Variability and Target Organ Injury in Rats with Sinoaortic Denervation

Julieta Del Mauro, Yanina Santander, Facundo M. Bertera, Andrea Carranza, Martin Donato, Susana Gorzalczany, Ricardo Gelpi, Carlos Taira, Christian Höcht

Abstract


Background: Increased blood pressure variability is a novel risk factor for the development of target organ injury both inhypertensive 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, bloodpressure 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 ofcarvedilol 30 mg/kg or vehicle. At the end of treatment, echocardiographic evaluation and blood pressure and short-term variabilitymeasurements were performed. Left ventricular and thoracic aortic weights were determined and histological sampleswere prepared from both tissues. Metalloproteinase MMP-2 and transforming growth factor b (TGF-b) were quantified in theleft ventricle and thoracic aorta.Results: Carvedilol reduced systolic blood pressure and its variability in sinoaortic-denervated rats compared with the controlgroup (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 wasfound in carvedilol-treated animals. The expression of TGF-b decreased in both organs after carvedilol treatment.Conclusions: Chronic carvedilol treatment significantly reduces systolic blood pressure and its short-term variability insinoaortic-denervated rats, decreasing the degree of left ventricular fibrosis.

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Revista argentina de cardiología. ISSN en línea 1850-3748. Argentine journal of cardiology (English ed. Online ISSN 2314-2286) Sociedad Argentina de Cardiología. Azcuénaga 980 (C1115AAD),Ciudad Autónoma de Buenos Aires, República Argentina. Tel. (54 11) 4961-6027/8/9 Fax: 4961-6020 www.sac.org.ar revista@sac.org.ar