Sildenafil citrate [viagra] induced enhancement of right atrial contractility in isolated rat heart in vitro

ABSTRACT

The present study deals with the chronotropic effects of Sildenafil citrate [Viagra] on right atrial contracctility of mammalian isolated heart muscle. Effects of Sildenafil citrate on rat isolated heart in-vitro using right atrial samples, in comparison with nor-adrenaline, revealed that Sildenafil at 10[-7] M and above produced dose related increases in contractility. The maximum observed increase at 10[-4] M represented a 126% +/- 31% increase above control amplitude. Nor-adrenaline produced similar dose-related increases in contractility and was appoximately three times more potent than Sildenafil citrate. Dimaprit also produced similar responses to the Sildenafil but was less potent. These results indicated that rat responds to Sildenafil citrate, which increases contracility and enhances atrial automaticity, with sensitivity comparable to that for nor-adrenaline. The selective antagonism of the Sildenafil contractility response by cimetidine indicated that this response is mediated via histamine H [2]-receptors and not H [1] noradrenergic beta receptors. The involvement of histamine H [2]- receptors is confirmed by the similarity of the response to dimaprit. The production of spontaneous contractions by dimaprit further suggests that Sildenafil citrate-induced enhancement of atrial automaticity is mediated via modified histamine H [2]-receptors