Nitric oxide and cardiac autonomic control in humans

Cardiac autonomic control is of prognostic significance in cardiac disease, yet the control mechanisms of this system remain poorly defined. Animal da ta suggest that nitric oxide (NO) modulates cardiac autonomic control. We i nvestigated the influence of NO on the baroreflex control of heart rate in healthy human subjects. In 26 healthy male volunteers (mean age, 23+/-5 yea rs), we measured heart rate variability and baroreflex sensitivity during i nhibition of endogenous NO production with N-G-monomethyl-L-arginine (L-NMM A) (3 mg/kg per hour) and during exogenous NO donation with sodium nitropru sside (1 to 3 mg/h). Increases from baseline (Delta) in high-frequency (HF) indexes of heart rate variability were smaller with L-NMMA in comparison t o an equipressor dose of the control vasoconstrictor phenylephrine (12 to 4 2 mu g/kg per hour): Delta root mean square of successive RR interval diffe rences (Delta RMSSD)=23+/-32 versus 51+/-8 ms (P<0.002); Delta percentage o f successive RR interval differences >50 ms (Delta pNN50)=5+/-15% versus 14 +/-12% (P<0.05); and Delta HF normalized power=-2+/-7 versus 9+/-8 normaliz ed units (P<0.01), respectively. Relative preservation of these indexes was observed during unloading of the baroreflex with sodium nitroprusside comp ared with a matched fall in blood pressure produced by a control vasodilato r, hydralazine (9 to 18 mg/h): Delta RMSSD=-8+/-8 versus -24+/-15 ms (P<0.0 01); Delta pNN50=-6+/-11% versus -15+/-19% (P<0.01); Delta HF normalized po wer=-7+/-13 versus -13+/-11 normalized units (P<0.05), respectively. The ch ange in cross-spectral alpha-index calculated as the square root of the rat io of RR interval power to systolic spectral power in the HF band (although not alpha-index calculated in the same way for the low-frequency bands or baroreflex sensitivity assessed by the phenylephrine bolus method) was atte nuated with L-NMMA compared with phenylephrine (Delta=4+/-8 versus 14+/-15 ms/mm Hg, respectively; P<0.02) and with sodium nitroprusside compared with hydralazine (Delta=-7+/-6 and -9+/-7 ms/mm Hg, respectively; P<0.05). In c onclusion, these data demonstrate that NO augments cardiac vagal control in humans.