CONICET | Buscador de Institutos y Recursos Humanos

Beta blockers have been traditionally considered as the first line therapy for hypertension. The aim of this study was to evaluate pharmacokinetics and cardiovascular effects of carvedilol (a beta blocker of third generation) in a hypertension model of aortic coarctation. Wistar male rats (380-420 g body weight) were subjected to coarctation of abdominal aorta (CoA) or a sham operation (SHAM). 7 days after the surgery, rats were injected i.v. with vehicle or carvedilol 5 mg kg-1 and blood pressure (BP) and heart rate were recorded immediately. At that time, CoA rats showed a significant loss of body weight and a lower left kidney weight/body weight ratio respect to SHAM rats. Basal mean arterial pressure of hypertensive rats (166±8 mmHg) was significantly higher than that of the sham operated rats (116±4 mmHg). After intravenous administration of carvedilol a biexponential decay of plasma carvedilol levels was found in both experimental groups compatible with a pharmacokinetic two-compartment model. The chronotropic response as well as the hypotensive response to carvedilol were not significantly different comparing CoA and SHAM rats. When studied the frequency components of blood pressure variability (BPV) (very low frequency-VLF, low frequency-LF and high frequency-HF), CoA rats showed greater BPV in the VLF range compared with SHAM animals, suggesting a compromise of renin-angiotensin system and myogenic vascular function in the regulation of BP. However, no difference was found in LF and HF variability between groups. On the other hand, carvedilol administration significantly reduced BPV in the three studied domains in SHAM and CoA rats. In conclusion, carvedilol exhibited increased hypotensive response in both experimental groups as a consequence of a greater inhibition of vascular sympathetic activity, although we did not find an overactivity of this system in this model of hypertension.