Exogenous L-arginine does not affect angiotensin II-induced renal vasoconstriction
It has been demonstrated that administration of the precursor of nitric oxide (NO) synthesis, l-arginine, can lower blood pressure and produce systemic and renal vasodilation in healthy human subjects and abrogates abnormal endothelium-dependent responses of pharmacological nitric oxide synthase inhibition in isolated vessels. In the renal vascular bed, which is particularly sensitive to endogenous NO synthesis, the vasoconstricting effect of pharmacologic NO-synthase inhibition was reversed by coinfusion of l-arginine.
Based on the suggestion that angiotensin II (ANG II) is the primary antagonist of NO-mediated vasodilation in the balance of factors regulating renal perfusion and the well established role of ANG II in the regulation of renovascular tone in healthy subjects and patients with hypertension, we hypothesised that exogenous l-arginine could influence an ANG II-mediated renal vasoconstriction if counterregulatory activation of NO synthesis is limited by substrate availability. We have therefore studied the effect of pretreatment or concomitant administration of l-arginine on increased renovascular resistance induced by exogenous ANG II-infusion in healthy male subjects.
Subject population
After approval of the study protocol by the Ethics Committee of Vienna University School of Medicine and written informed consent, 17 healthy, non-smoking, drug-free male volunteers between 20 and 32 years of age were studied. Each subject passed a screening examination that included history and physical examination, 12-lead electrocardiogram, complete blood cell count with differential, 24 h creatinine clearance and urinalysis, urine drug screen, serum electrolytes, bilirubin, BUN, creatinine, cholesterol, triglycerides, γ-glutamyltransferase, glucose, lactate dehydrogenase, ASAT, ALAT, total protein, activated partial thromboplastin time, thrombin time, hepatitis A, B, C serologic tests and human immunodeficiency virus antibody tests.
Study protocol
The study was conducted according to two different trial protocols. Both protocols followed a double-blind, randomised, two-way cross-over design with washout periods between study days of at least 5 days.
Filed under: Clinical Pharmacology