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Effect of sildenafil on the isolated rat aortic rings.
Fundam Clin Pharmacol. 2005 Aug; 19(4):449-56.FC

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+Show Affiliations

Department of Pharmacology, Faculty of Pharmacy, University of Alexandria, El-Khartoom Square, Alexandria, Egypt. fmsharabi@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16011732

Citation

Sharabi, F M., et al. "Effect of Sildenafil On the Isolated Rat Aortic Rings." Fundamental & Clinical Pharmacology, vol. 19, no. 4, 2005, pp. 449-56.
Sharabi FM, Daabees TT, El-Metwally MA, et al. Effect of sildenafil on the isolated rat aortic rings. Fundam Clin Pharmacol. 2005;19(4):449-56.
Sharabi, F. M., Daabees, T. T., El-Metwally, M. A., & Senbel, A. M. (2005). Effect of sildenafil on the isolated rat aortic rings. Fundamental & Clinical Pharmacology, 19(4), 449-56.
Sharabi FM, et al. Effect of Sildenafil On the Isolated Rat Aortic Rings. Fundam Clin Pharmacol. 2005;19(4):449-56. PubMed PMID: 16011732.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of sildenafil on the isolated rat aortic rings. AU - Sharabi,F M, AU - Daabees,T T, AU - El-Metwally,M A, AU - Senbel,A M, PY - 2005/7/14/pubmed PY - 2005/9/16/medline PY - 2005/7/14/entrez SP - 449 EP - 56 JF - Fundamental & clinical pharmacology JO - Fundam Clin Pharmacol VL - 19 IS - 4 N2 - 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. SN - 0767-3981 UR - https://www.unboundmedicine.com/medline/citation/16011732/Effect_of_sildenafil_on_the_isolated_rat_aortic_rings_ L2 - https://doi.org/10.1111/j.1472-8206.2005.00345.x DB - PRIME DP - Unbound Medicine ER -