Open AccessPhenylephrine Induces Endogenous Noradrenaline Release in the Rat Vas deferens through Nitric Oxide Synthase Pathway
Author(s) -
Pinto Rui,
Barrento Clara,
MotaFilipe Helder,
Lima Beatriz Silva
Publication year - 2003
Publication title -
pharmacology & toxicology
Language(s) - English
Resource type - Journals
eISSN - 1600-0773
pISSN - 0901-9928
DOI - 10.1034/j.1600-0773.2003.930407.x
Subject(s) - phenylephrine , prazosin , reserpine , vas deferens , omega n methylarginine , nitric oxide , medicine , endocrinology , nitric oxide synthase , chemistry , contractility , yohimbine , pharmacology , antagonist , blood pressure , receptor
Abstract: We 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 N G ‐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 α 1 ‐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 E max 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 μM 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 α 1 ‐adrenoceptors.