title: Role of nitric oxide formation in the regulation of haemodynamics and the release of noradrenaline and adrenaline.
abstract: This study in the anaesthetized rabbit aimed at determining the role of nitric oxide (NO), the putative endothelium-derived relaxing factor, in the regulation of haemodynamics and the release into plasma of noradrenaline and adrenaline. Specific inhibition of NO formation was achieved by i.v. bolus injection of L-NG-monomethyl-arginine (L-NMMA; 3-100 mg kg-1). Phenylephrine was infused i.v. at constant rates (2.5-20 micrograms kg-1 min-1) in order to assess baroreflex-mediated changes in release due to direct peripheral vasoconstriction. Rates of noradrenaline and adrenaline release into plasma were determined by the radio-tracer technique. L-NMMA, but not D-NMMA, dose-dependently increased mean arterial pressure and total peripheral vascular resistance, whereas both heart rate and cardiac output decreased concomitantly. The corresponding ED50 values for L-NMMA ranged from 11.2 to 18.5 mg kg-1. Inhibition of NO formation by L-NMMA as well as phenylephrine infusion caused decreases in the plasma clearance of noradrenaline and adrenaline which were correlated with the drug-induced decreases in cardiac output. Both L-NMMA and phenylephrine reduced the rate of noradrenaline release into plasma as they increased total peripheral resistance. Moreover, the curvilinear relationship between these two parameters obtained for L-NMMA was virtually identical to that produced by phenylephrine, indicating that the reduction in noradrenaline release by L-NMMA is mediated solely by the baroreflex. From the L-NMMA-induced maximum inhibition of noradrenaline release, it is concluded that the counter-regulation against peripheral vasodilation by NO accounts for 69% of basal noradrenaline release.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Institut für Pharmakologie und Toxikologie, Universität Würzburg, Federal Republic of Germany.
authors.forename: T
authors.initials: T
authors.lastname: Halbrügge
authors.forename: K
authors.initials: K
authors.lastname: Lütsch
authors.forename: A
authors.initials: A
authors.lastname: Thyen
authors.forename: K H
authors.initials: KH
authors.lastname: Graefe
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004837:Epinephrine / Q000097:blood / Q000378:metabolism*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology*; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D019323:omega-N-Methylarginine
chemical_list: D010656:Phenylephrine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D009638:Norepinephrine; D004837:Epinephrine