Nitric Oxide and Cardiac Autonomic Control in Humans

Abstract

Abstract —Cardiac autonomic control is of prognostic significance in cardiac disease, yet the control mechanisms of this system remain poorly defined. Animal data suggest that nitric oxide (NO) modulates cardiac autonomic control. We investigated the influence of NO on the baroreflex control of heart rate in healthy human subjects. In 26 healthy male volunteers (mean age, 23±5 years), we measured heart rate variability and baroreflex sensitivity during inhibition of endogenous NO production with N G -monomethyl- l -arginine (L-NMMA) (3 mg/kg per hour) and during exogenous NO donation with sodium nitroprusside (1 to 3 mg/h). Increases from baseline (Δ) in high-frequency (HF) indexes of heart rate variability were smaller with L-NMMA in comparison to an equipressor dose of the control vasoconstrictor phenylephrine (12 to 42 μg/kg per hour): Δroot mean square of successive RR interval differences (ΔRMSSD)=23±32 versus 51±48 ms ( P <0.002); Δpercentage of successive RR interval differences >50 ms (ΔpNN50)=5±15% versus 14±12% ( P <0.05); and ΔHF normalized power=−2±7 versus 9±8 normalized units ( P <0.01), respectively. Relative preservation of these indexes was observed during unloading of the baroreflex with sodium nitroprusside compared with a matched fall in blood pressure produced by a control vasodilator, hydralazine (9 to 18 mg/h): ΔRMSSD=−8±8 versus −24±15 ms ( P <0.001); ΔpNN50=−6±11% versus −15±19% ( P <0.01); ΔHF normalized power=−7±13 versus −13±11 normalized units ( P <0.05), respectively. The change in cross-spectral α-index calculated as the square root of the ratio of RR interval power to systolic spectral power in the HF band (although not α-index calculated in the same way for the low-frequency bands or baroreflex sensitivity assessed by the phenylephrine bolus method) was attenuated with L-NMMA compared with phenylephrine (Δ=4±8 versus 14±15 ms/mm Hg, respectively; P <0.02) and with sodium nitroprusside compared with hydralazine (Δ=−7±6 and −9±7 ms/mm Hg, respectively; P <0.05). In conclusion, these data demonstrate that NO augments cardiac vagal control in humans.