Phenylephrine induces endogenous noradrenaline release in the rat vas deferens through nitric oxide synthase pathway.
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.
Pinto
Rui
R
Unit of Pharmacology and Pharmacotoxicology, Faculty of Pharmacy. University of Lisbon, and Clinical Laboratory of Dr. Joaquim Chaves, Algés, Portugal.
Barrento
Clara
C
Mota-Filipe
Helder
H
Lima
Beatriz Silva
BS
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
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