Efeito da inibição da fosfodiesterase-5 sobre as propriedades de transdução dinâmica do nervo vago cardíaco em ratos espontaneamente hipertensos.

Abstract

Recent data have reported that sildenafil citrate, an inhibitor of phosphodiesterase-5 (PDE-5), widely used in the treatment of erectile dysfunction, causes vasodilation and reflex sympathetic activation, which may enhance cardiovascular risk. However, the effects of sildenafil citrate on cardiac vagal parasympathetic control, in the arterial hypertension context, have not been yet elucidated. The aim of the present study was to evaluate the effects of the acute treatment with sildenafil citrate on the dynamic transduction properties of the cardiac vagus nerve in spontaneously hypertensive rats (SHR) comparing with their normotensive controls, the Wistar-Kyoto (WKY) rats. Thirty nine male 20-weeks old rats were divided in four experimental groups: group WKY control (n=9); group WKY treated (n=10); group SHR control (n=10) and group SHR treated (n=10). All animals, after anesthesia with sodium pentobarbital (40 mg/Kg, i.p.), were submitted to surgical procedure in order to implant canula into the left common carotid artery (for arterial blood pressure recordings) and isolation of right cervical vagus nerve (for electrical stimulation). After baseline recording during five minutes followed by propranolol administration (4 mg/Kg, i.v.) and another 5 minutes arterial pressure recording period, the animals, according to their groups, received sildenafil citrate (1mg/Kg, i.v.) or saline (1 mL/Kg). The dynamic stimulation of vagus nerve, in the frequency ranges from 0,1 to 2,0Hz, was performed and analyzed by means of transfer function analysis, which permit to calculate in the frequency domain the coherence, the phase shift and the magnitude of the transfer function between nervous stimulus (input signal) and pulse interval response (output signal) in the low (LF=0,1-0,8Hz) and high frequency ranges (HF=1,0-2,0Hz). The acute treatment with sildenafil citrate caused a significant arterial hypotension in both normotensive and hypertensive animals, being more intensive in hypertensive animals. In these animals, the marked arterial hypotension was associated to a light tachycardic response, which was not observed in normotensive rats. Regarding to dynamic electrical stimulation of the cardiac vagus nerve, although the transfer function magnitude (dynamic gain) in control SHRs was higher (20,9±4,06ms/Hz in LF range and 11,1±2,4ms/Hz in HF range) than that observed in control WKY rats (12,1±4,3ms/Hz in LF range and 3,9±2,5ms/Hz in HF range, p<0,05), the treatment with sildenafil citrate was not able to change the values of transfer function magnitude, as well as coherence and phase shift in both SHR and WKY rats. These data indicate that acute sildenafil citrate, in both normotensive and hypertensive rats, does not modify the dynamic transdution properties of the peripheral cardiac vagus nerve, suggesting that phosphodiesterase-5 does not play a significant role in the dynamic modulation of the peripheral cardiac vagal parasympathetic function in rats.