• Rui Pinto, Clara Barrento, Helder Mota-Filipe, and Beatriz Silva Lima.
• Unit of Pharmacology and Pharmacotoxicology, Faculty of Pharmacy. University of Lisbon, and Clinical Laboratory of Dr. Joaquim Chaves, Algés, Portugal.
• Pharmacol. Toxicol. 2003 Oct 1;93(4):191-6.

AbstractWe have previously observed that in the rat vas deferens nitric oxide synthase pathway potentiated phenylephrine-induced contractility raising the possibility of a facilitatory role on neurotransmission by nitric oxide. To confirm this hypothesis we studied the effect of phenylephrine on the concentration response curves obtained in preparations from reserpine-treated rats in the absence and presence of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). The endogenous noradrenaline released by normal preparations (without reserpine) was measured in the perfusion fluid of preparations stimulated with phenylephrine, in the absence and presence of L-NMMA, L-NMMA + the nitric oxide donor 3-morpholinosydnonimine hydrochloride (SIN-1), the alpha1-adrenoceptor antagonist prazosin and the blocker of noradrenaline carrier desipramine. The phenylephrine-induced noradrenaline release in a calcium-free medium was also measured. L-NMMA decreased the Emax of phenylephrine concentration response curves obtained in preparations from normal (reserpine-untreated) but not from reserpine-treated rats. In the perfusion fluid of preparations incubated with phenylephrine, a concentration-dependent increase of noradrenaline was observed which was reversed by L-NMMA and restored when SIN-1 was added together with the nitric oxide synthase inhibitor. The concentration-dependent phenylephrine-induced noradrenaline increase was not modified by desipramine but was abolished by 10 microM prazosin. In calcium-free medium, phenylephrine failed to increase the noradrenaline concentration. These results suggest that in the rat vas deferens, nitric oxide pathway potentiates the phenylephrine-induced contractility through a mechanism which involves calcium-dependent release of endogenous noradrenaline and seems to depend, at least partially on the activation of alpha1-adrenoceptors.

40 keywords...

hide…