What is the action of viagra on CVS, and on what receptors it acts?

Sildenafil (Viagra) is a highly selective and potent inhibitor of the breakdown of guanosine 3,5,-cyclic monophosphate (cGMP) by its specific phosphodiesterase isoenzyme (PDE5; Wallis et al., 1999), and is used in the treatment of erectile dysfunction (recently reviewed by Gresser %26amp; Gleiter, 2002). Questions arose about the safety of the drug in patients with ischaemic heart disease and anecdotal reports of cardiovascular deaths associated with its use generated early concern, although a recent review came to the conclusion that the 'number of deaths potentially associated with sildenafil appears to be extremely small' (Cheitlin et al., 1999), even though there were 130 reported cases of cardiac death in the U.S. alone in the initial 6-month period of its use. The fact that sildenafil prolongs cardiac repolarisation by blocking the rapid component of the delayed rectifier current Ik, and the fact that this may lead to triggered ventricular arrhythmias including fibrillation (Priori, 1998), has led to the suggestion that this may be a possible mechanism of the few reported cases of sudden cardiac death that have been associated with sildenafil usage (Geelen et al., 2000).





More recently, there have been reports that sildenafil may protect the myocardium by mechanisms similar to those thought to be responsible for the cardioprotective effects of ischaemic preconditioning. Thus, in rabbits, sildenafil given intravenously 1 h, and orally 24 h, prior to acute coronary artery occlusion, reduced the infarct size through a mechanism that involved the opening of mitochondrial KATP channels, since the protection was blocked by 5-hydroxydecanoate (Ockaili et al., 2002). In mice, this protection is mediated by nitric oxide (NO); there was evidence for increases in both eNOS and, later, iNOS and a selective inhibitor of iNOS (1400W) abolished the delayed sildenafil-induced reduction in infarct size (Salloum et al., 2003). These mechanisms are reminiscent of NO involvement in mediating the early protection afforded by brief periods of coronary artery occlusion (ischaemic preconditioning; Végh et al., 1992a) and the delayed protection by brief periods of ischaemia and by cardiac pacing (Végh et al., 1994; Qui et al., 1997, Kis et al., 1999), both of which are also mediated by NO. The fact that cGMP levels are increased under these conditions is also consistent with the finding that inhibitors of guanylyl cyclase prevent the early (Végh et al., 1992b) and late (Kodani et al., 2002) effects of ischaemic preconditioning. This led to the suggestion to examine whether selective inhibition of the PDE enzyme responsible for its breakdown is, like preconditioning, a powerful antiarrhythmic procedure (Végh et al., 1992b). This suggestion is explored in the present report.





To our knowledge, there have been no studies examining the effects of orally administered sildenafil on the severity of those life-threatening ventricular arrhythmias that arise early after acute coronary occlusion and that are implicated in some cases of sudden cardiac death in the clinical situation. The present study examines the effects of orally administered sildenafil in an established large animal model of ischaemia and reperfusion-induced arrhythmias.

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