Exogenous L‐Arginine Restores Spontaneous Cardiac Baroreflex Sensitivity in Never‐Treated Hypertensive Men

Abstract

Depressed cardiac baroreflex sensitivity (cBRS) is associated with an increased risk of mortality in patients with hypertension. A candidate mechanism for the centrally mediated impairment in cBRS is reduced synthesis of the neuromodulator nitric oxide. Therefore, we investigated the effect of intravenous L‐arginine, a precursor of nitric oxide, on the cBRS in human hypertension. Beat‐to‐beat blood pressure (Finometer) and heart rate (ECG) were measured in both normotensive (n=8, 44±4 yrs., Norm) and never‐treated hypertensive men (n=8, 47±2 yrs., Hyper) before and during intravenous infusion of L‐arginine (1 g/min; total, 30 g) or saline. Linear regression analysis between RR interval and systolic blood pressure was used to determine the gain (i.e. sensitivity) of the arterial baroreflex control of the heart. Compared to Norm group, patients with hypertension had lower spontaneous cBRS (Norm: 13±1 vs. Hyper: 7.9±1 ms.mmHg‐1; P<0.01). On administration of L‐arginine, cBRS increased in both groups (Norm: 17±3 vs. Hyper: 15±3 ms.mmHg‐1; P<0.01 vs. before infusion) and returned to near resting values after infusion. Increases in cBRS during infusion of L‐arginine were greater in Hyper (P<0.05) and differences between groups disappeared. Importantly, during saline infusion, the spontaneous cBRS remained unchanged in both groups. In conclusion, these data demonstrate that short‐term L‐arginine infusion restores the arterial baroreflex control of heart rate in never‐treated hypertensive men, probably via increased nitric oxide synthesis.