Influence of basal nitric oxide secretion on cardiac function in man. 1995

P B Clarkson, and P O Lim, and T M MacDonald
University Department of Clinical Pharmacology, Ninewells Hospital & Medical School, Dundee, Scotland, UK.

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.

UI MeSH Term Description Entries
D008297 Male Males
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D010919 Placebos Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol. Sham Treatment
D012016 Reference Values The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D004311 Double-Blind Method A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment. Double-Masked Study,Double-Blind Study,Double-Masked Method,Double Blind Method,Double Blind Study,Double Masked Method,Double Masked Study,Double-Blind Methods,Double-Blind Studies,Double-Masked Methods,Double-Masked Studies,Method, Double-Blind,Method, Double-Masked,Methods, Double-Blind,Methods, Double-Masked,Studies, Double-Blind,Studies, Double-Masked,Study, Double-Blind,Study, Double-Masked
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

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