Role of nitric oxide formation in the regulation of haemodynamics and the release of noradrenaline and adrenaline.
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)
Halbrügge
T
T
Institut für Pharmakologie und Toxikologie, Universität Würzburg, Federal Republic of Germany.
Lütsch
K
K
Thyen
A
A
Graefe
K H
KH
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
D010656:Phenylephrine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D009638:Norepinephrine; D004837:Epinephrine