Acute supplementation with the nitric oxide precursor L-arginine does not improve cardiovascular performance in patients with hypercholesterolemia.
Endothelial dysfunction based on lack of nitric oxide (NO) may contribute to several settings of cardiovascular disorder. Chronic oral supplementation with the NO precursor L-arginine counteracts the development of aortic atherosclerosis in cholesterol-fed rabbits, and i.v. infusion of L-arginine may acutely improve endothelium-dependent coronary epicardial vasodilation in patients with hypercholesterolemia (HC). To clarify whether excess NO precursor may also improve general cardiovascular performance in HC, we measured working capacity indices of myocardial ischemia, and basal and post-occlusive forearm and skin blood flow in nine patients with elevated plasma cholesterol (9.1 +/- 0.2 mumol/l) following random double-blinded administration of L-arginine (16 g i.v.) or placebo. Infusion of L-arginine raised the plasma concentration of this amino acid from 85 +/- 12 to 2460 +/- 230 mumol/l but did not change the plasma level of the major NO metabolite nitrate. Maximal working capacity, indices of myocardial ischemia, and basal and post-occlusive blood flow in the skin or forearm did not differ between the treatments. The lack of positive effect of L-arginine compared to placebo indicates that excess NO precursor did not improve microvascular endothelial function in the patients, or alternatively, that the indices measured in the present study were not dependent on endothelial microvessel function. Thus, in patients with HC, deficiency of precursor for NO formation does not seem to impair either maximal exercise capacity myocardial perfusion during maximal exercise, or maximal vasodilator capacity in skeletal muscle or skin.
Wennmalm
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Department of Clinical Physiology, Göteborg University, Sahlgrenska University Hospital, Sweden.
Edlund
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Granström
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EF
Wiklund
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O
D001120:Arginine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001132:Arm / Q000098:blood supply; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000378:metabolism*; D005080:Exercise Test; D005260:Female; D006334:Heart Function Tests / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000503:physiopathology*; D006940:Hyperemia / Q000209:etiology / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000209:etiology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis*; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
D008055:Lipids; D009566:Nitrates; D009569:Nitric Oxide; D001120:Arginine