AIMS: It has been suggested that provision of the substrate of nitric oxide (NO) synthesis, L-arginine, might influence the effects of renal vasoconstrictors. We have therefore studied the effects of pretreatment or concomitant administration of L-arginine on angiotensin II (ANG II)-increased renovascular resistance. METHODS: The study was conducted in a double-blind, randomized, cross-over design. Eight healthy subjects were assigned to placebo or a continuous intravenous coinfusion of ANG II (5.0 ng kg[-1] min[-1], infusion period 75 min) with L-arginine (17 mg kg[-1] min[-1], infusion period 30 min). Nine further subjects received a continuous infusion of ANG II with or without pretreatment of L-arginine. Changes in renal plasma flow (RPF) were estimated by the steady state clearance of PAH. RESULTS:L-arginine alone increased RPF to 110 +/- 10% over baseline (P < 0.003). The ANG II-induced decrease in RPF was not affected by pretreatment or coinfusion of L-arginine. CONCLUSIONS: Our results demonstrate that a counterregulatory response of the renal vasculature to high levels of ANG II does not depend on exogenous L-arginine. In healthy subjects, this lack of functional antagonism at the renal vasculature is therefore not a result of NO substrate availability.
RCT Entities:
AIMS: It has been suggested that provision of the substrate of nitric oxide (NO) synthesis, L-arginine, might influence the effects of renal vasoconstrictors. We have therefore studied the effects of pretreatment or concomitant administration of L-arginine on angiotensin II (ANG II)-increased renovascular resistance. METHODS: The study was conducted in a double-blind, randomized, cross-over design. Eight healthy subjects were assigned to placebo or a continuous intravenous coinfusion of ANG II (5.0 ng kg[-1] min[-1], infusion period 75 min) with L-arginine (17 mg kg[-1] min[-1], infusion period 30 min). Nine further subjects received a continuous infusion of ANG II with or without pretreatment of L-arginine. Changes in renal plasma flow (RPF) were estimated by the steady state clearance of PAH. RESULTS:L-arginine alone increased RPF to 110 +/- 10% over baseline (P < 0.003). The ANG II-induced decrease in RPF was not affected by pretreatment or coinfusion of L-arginine. CONCLUSIONS: Our results demonstrate that a counterregulatory response of the renal vasculature to high levels of ANG II does not depend on exogenous L-arginine. In healthy subjects, this lack of functional antagonism at the renal vasculature is therefore not a result of NO substrate availability.
Authors: M A Munger; M Chance; R Nair; A W Prescott; A R Nara; M S Simonson; J A Green; E L Posvar Journal: J Clin Pharmacol Date: 1992-01 Impact factor: 3.126