title: Phenylephrine induces endogenous noradrenaline release in the rat vas deferens through nitric oxide synthase pathway.
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 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.
authors: Unit of Pharmacology and Pharmacotoxicology, Faculty of Pharmacy. University of Lisbon, and Clinical Laboratory of Dr. Joaquim Chaves, Algés, Portugal.
authors: Rui
authors: R
authors: Pinto
authors: Clara
authors: C
authors: Barrento
authors: Helder
authors: H
authors: Mota-Filipe
authors: Beatriz Silva
authors: BS
authors: Lima
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D058646:Adrenergic alpha-1 Receptor Agonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003891:Desipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009638:Norepinephrine / Q000096:biosynthesis*; D010656:Phenylephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D058646:Adrenergic alpha-1 Receptor Agonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D003891:Desipramine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D011224:Prazosin