Enhancement of the vasoconstrictor response to KCL by nitric oxide synthesis inhibition: a comparison with noradrenaline.
The role of the vascular endothelium in the response to a vasoconstrictor agent acting through a non-receptorial mechanism, such as KCl, was tested in the isolated mesenteric vascular bed of the rat. It was confirmed that the vasoconstrictor response evoked by stimulation of sympathetic terminals was unaffected by 100 microM NG-nitro-D-arginine methyl ester (D-NAME), but was significantly potentiated by 100 microM NG-nitro-L-arginine methyl ester (L-NAME) and by removal of endothelium. Responses to exogenous noradrenaline (1-100 microM) were also enhanced by treatment with 100 microM NG-monomethyl-L-arginine (L-NMMA) and with L-NAME, but not with D-NAME. The potentiating effect of NO synthesis inhibitors was reversed by 1 mM L-arginine. Moreover, the noradrenaline-induced vasoconstriction was significantly increased by endothelium-deprivation. Potassium chloride (80 mM) induced a vasoconstrictor response which was not modified by pretreatment with prazosin (0.1 microM) and yohimbine (0.1 microM). The response to KCl was unaffected by D-NAME (100 microM) but the L-stereoisomer induced a significant increase in the perfusion pressure. In endothelium-denuded preparations the vasoconstrictor response to KCl was greater than in control conditions and was quantitatively similar to that observed in L-NAME-treated preparations. The responses to electrical field stimulation, noradrenaline and KCl in endothelium-denuded preparations were not modified by L-NAME. The results suggest that an increase in vascular tone, per se, may represent a trigger for the release of endothelium-derived relaxing factor from endothelial cells.
Amerini
S
S
Department of Pharmacology, University of Florence, Italy.
Mantelli
L
L
Ledda
F
F
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009638:Norepinephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D011189:Potassium Chloride; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine