| Abstract | 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. |
| Authors | F M Sharabi, T T Daabees, M A El-Metwally, A M Senbel
(Affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Alexandria, El-Khartoom Square, Alexandria, Egypt. fmsharabi at hotmail.com)
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| Journal | Fundamental & clinical pharmacology
(Fundam Clin Pharmacol)
Vol. 19
Issue 4
Pg. 449-56
(Aug 2005)
ISSN: 0767-3981 England |
| PMID | 16011732
(Publication Type: In Vitro, Journal Article)
|
| Chemical References |
- Phosphodiesterase Inhibitors
- Piperazines
- Purines
- Sulfones
- Nitric Oxide
- sildenafil
- Nitroprusside
- omega-N-Methylarginine
- Acetylcholine
- Cyclic GMP
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| Topics |
- Acetylcholine
(pharmacology)
- Animals
- Aorta, Thoracic
(drug effects, physiology)
- Cyclic GMP
(physiology)
- Male
- Nitric Oxide
(physiology)
- Nitroprusside
(pharmacology)
- Phosphodiesterase Inhibitors
(pharmacology)
- Piperazines
(pharmacology)
- Purines
- Rats
- Sulfones
- Vasodilation
(drug effects)
- omega-N-Methylarginine
(pharmacology)
|
