L-arginine augments cardiac vagal control in healthy human subjects.
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.
Chowdhary
Saqib
S
Department of Cardiovascular Medicine, University of Birmingham, Birmingham, United Kingdom. S.Chowdhary@bham.ac.uk
Nuttall
Sarah L
SL
Coote
John H
JH
Townend
Jonathan N
JN
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
D014665:Vasodilator Agents; D006830:Hydralazine; D009569:Nitric Oxide; D001120:Arginine