Sildenafil inhibits agonist-evoked rat uterine contractility: influence of guanylyl cyclase inhibition.
Sildenafil shows a potent relaxant effect on corpus cavernosum smooth muscles by prolonging cyclic guanosine monophosphate (cGMP) actions. We investigated whether this inhibitory effect of sildenafil was also displayed on the uterine musculature. Isolated uteri of non-pregnant rats were used to measure the possible sildenafil-induced inhibition of contractions evoked by various oxytocic agents, viz., prostaglandin E2, oxytocin and acetylcholine. The relation of these effects to sildenafil action on cGMP was also examined, using methylene blue as a guanylyl cyclase inhibitor. Sildenafil (30 and 100 nM) was found to shift to the right the non-cumulative concentration-response curves of the test agonists in a concentration-dependent manner. The shift was accompanied by a reduction in the maximal response of the tissue to all uterine stimulants selected. Sildenafil also elicited a marked concentration-dependent increase in EC25 of prostaglandin E2, oxytocin and acetylcholine, as compared to their respective control values. Preincubation of the uterine strip with methylene blue (10 microM) reduced the inhibitory effects of sildenafil on oxytocin- and acetylcholine-evoked contractions, at submaximal concentrations of each agonist. The results suggest that sildenafil inhibits the uterotonic potentials of various oxytocic agents and that this effect could be probably related to the drug's action on cGMP.
Agha
A M
AM
Department of Pharmacology, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, 11562, Cairo, Egypt. azzaagha@hotmail.com
Taha
R A
RA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D010120:Oxytocics / Q000494:pharmacology*; D010121:Oxytocin / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D051381:Rats; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D013450:Sulfones; D014599:Uterus / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010120:Oxytocics; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D010121:Oxytocin; D000068677:Sildenafil Citrate; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D015232:Dinoprostone; D000109:Acetylcholine; D008751:Methylene Blue