title: L-arginine augments cardiac vagal control in healthy human subjects.
abstract: Cardiac vagal control has prognostic significance in cardiac disease, but the control mechanisms of this system remain poorly understood. We have previously demonstrated a role for NO in promoting vagal control of heart rate in humans. Here we examine the influence of L-arginine, the substrate for NO synthase, on this mechanism in healthy human subjects. Eleven healthy volunteers (9 men; age, 20 to 25 years) underwent measurement of heart rate variability and baroreflex sensitivity before and during a systemic infusion of L-arginine (1 g/min; total, 30 g). To control for the fall in blood pressure, comparison was made with an infusion of the control vasodilator hydralazine. Stereospecificity of observed effects was investigated by infusion of D-arginine. Urinary nitrate and nitrite (NO(x)) and cGMP concentrations were measured as indexes of NO generation. L-Arginine infusion produced a drop in mean arterial pressure of 5 mm Hg. This fall in blood pressure was matched by hydralazine infusion and was not observed with either D-arginine or saline infusion. Although RR interval duration, heart rate variability, and baroreflex sensitivity all fell significantly with hydralazine, the same degree of baroreflex unloading with L-arginine produced an increase in RR interval duration and no change or even slight increases in heart rate variability and baroreflex sensitivity. In contrast, D-arginine produced falls in high-frequency indexes of heart rate variability compared with saline. Only L-arginine increased urinary NO(x) and cGMP excretion. In conclusion, these data demonstrate that short-term L-arginine infusion facilitates vagal control of heart rate in healthy humans, probably via increased NO synthesis.
authors.affiliation: Department of Cardiovascular Medicine, University of Birmingham, Birmingham, United Kingdom. S.Chowdhary@bham.ac.uk
authors.forename: Saqib
authors.initials: S
authors.lastname: Chowdhary
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Nuttall
authors.forename: John H
authors.initials: JH
authors.lastname: Coote
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Townend
mesh_terms: D000328:Adult; D001120:Arginine / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D016037:Single-Blind Method; D013237:Stereoisomerism; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D006830:Hydralazine; D009569:Nitric Oxide; D001120:Arginine