Sildenafil, a highly selective inhibitor of PDE 5, is effective in the treatment of
erectile dysfunction. Penile erection involves relaxation of smooth muscle of corpus cavernosum and its associated arterioles. The objective of this study was to investigate the effect of
sildenafil on
nitric oxide/cyclic
guanosine monophosphate (NO/cGMP)-dependent relaxation of rat aortic rings. The contribution of
sildenafil to the vasorelaxation of rat aortic rings was also investigated.
Sildenafil produced significant potentiation of
acetylcholine (ACh, 2 x 10(-6) m)-induced relaxation at concentration > or =1 x 10(-8) m. Addition of
sildenafil (1 x 10(-7) m) to aortic rings failed to alter the effect of N(G)-nitro-
L-arginine (l-NNA, 3 x 10(-5) m) or
methylene blue (
MB, 3 x 10(-5) m) on ACh response. Similarly,
sildenafil (1 x 10(-7) m) augmented significantly the vasorelaxation induced by
sodium nitroprusside over the range of 1 x 10(-9)-1 x 10(-8) m. When added to
phenylephrine (3 x 10(-6) m)-precontracted rat aortic rings,
sildenafil (1 x 10(-9)-1 x 10(-4) m) induced concentration-dependent relaxation reaching a maximum of 96.48 +/- 1.44%. These relaxations were not significantly attenuated by previous incubation with L-NNA (3 x 10(-5) m) or
MB (3 x 10(-5) m). Denudation did not significantly affect the
vasorelaxant effect of
sildenafil.
Sildenafil may act in the rat aortic rings through the amplification of NO/cGMP pathway. It may augment both basal endothelial NO function and exogenous NO-dependent vasodilatation. However,
sildenafil may act by a mechanism independent of NO/cGMP pathway and this mechanism contributes to its smooth muscle relaxant effect.