Influence of basal nitric oxide secretion on cardiac function in man.
1. Nitric oxide is recognised as an important biological mediator, which is thought to be involved in cardiovascular homeostasis. The purpose of this study was to investigate the effects of basal nitric oxide synthesis on cardiac function in man, by blocking nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA). 2. Eight normal volunteers were studied on two separate occasions. Measurements of heart rate, blood pressure and echocardiographic indices of left ventricular systolic and diastolic function were made at baseline on each day and every 20 min during incremental infusion of L-NMMA (0.1, 0.2, 0.5, 1.0 and 2.0 mg kg-1 h-1) or placebo. 3. A trend towards reduction in heart rate was observed with L-NMMA infusion although this did not reach statistical significance, whereas significant increases in both systolic blood pressure (at 2.0 mg kg-1 h-1) and systemic vascular resistance index (at 0.5 mg kg-1 h-1) were seen. 4. L-NMMA infusion caused significant reductions in stroke distance and cardiac index, although there was no change in the ratio of end systolic wall stress/end systolic volume index (an afterload independent index of left ventricular systolic performance). 5. The isovolumic relaxation time significantly increased with L-NMMA infusion, together with a significant reduction in the 'E' wave flow velocity integral. Reductions in both peak E/A ratio and E/A flow velocity integral ratio were also seen, although these failed to reach statistical significance. 6. In conclusion, the basal generation of nitric oxide in man appears to maintain a vasodilated state, and modifies left ventricular diastolic filling parameters.
Clarkson
P B
PB
University Department of Clinical Pharmacology, Ninewells Hospital & Medical School, Dundee, Scotland, UK.
Lim
P O
PO
MacDonald
T M
TM
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004311:Double-Blind Method; D016232:Endothelins / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010919:Placebos; D012016:Reference Values; D019323:omega-N-Methylarginine
D016232:Endothelins; D004791:Enzyme Inhibitors; D010919:Placebos; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase