L-arginine infusion decreases peripheral arterial resistance and inhibits platelet aggregation in healthy subjects.
1. L-Arginine is the physiological precursor of nitric oxide which induces vasodilatation and inhibits platelet aggregation by the formation of cyclic GMP. 2. In the present study we investigated the effects of an intravenous infusion of L-arginine (30 g, 30 min) compared with placebo on blood pressure, heart rate and peripheral haemodynamics in ten healthy male subjects. Cyclic GMP, NO2- and NO3- were determined in plasma and urine to assess NO production in vivo by a new, highly specific and sensitive gas chromatography-mass spectrometry method. 3. L-Arginine significantly decreased mean arterial blood pressure and increased heart rate. The effect was more pronounced on diastolic than on systolic blood pressure. This was due to a decreased peripheral arteriolar resistance, as in femoral artery Doppler sonography the arterial diameter was unchanged but blood flow was increased. These haemodynamic effects were not observed after placebo administration. 4. Urinary excretion of cyclic GMP increased by 65.4% after L-arginine and by 25.1 after placebo. Urinary NO2- excretion was near the threshold of detection. Urinary NO3- excretion increased by 79.7% after L-arginine. Plasma arginine levels increased nearly ten-fold after the L-arginine infusion, and plasma cyclic GMP increased by a similar rate as in urine. However, plasma NO2- and NO3- remained unchanged after both treatments, as did plasma alpha-atrial natriuretic peptide levels. 5. Platelet aggregation was inhibited by 32.7% after L-arginine (P < 0.05), but was unchanged after placebo. Platelet intracellular cyclic GMP was increased by 43.0% after L-arginine, but not after placebo (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Clinical Pharmacology, Hannover Medical School, Federal Republic of Germany.
S M
SM
Bode-Böger
R H
RH
Böger
A
A
Creutzig
D
D
Tsikas
F M
FM
Gutzki
K
K
Alexander
J C
JC
Frölich
D000328:Adult; D001120:Arginine / Q000097:blood / Q000494:pharmacology*; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D004311:Double-Blind Method; D008401:Gas Chromatography-Mass Spectrometry; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009566:Nitrates / Q000097:blood / Q000652:urine; D009573:Nitrites / Q000097:blood / Q000652:urine; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*
D009566:Nitrates; D009573:Nitrites; D010975:Platelet Aggregation Inhibitors; D001120:Arginine; D006152:Cyclic GMP