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, 23Ϯ5 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 (⌬) 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 g/kg per hour): ⌬root mean square of successive RR interval differences (⌬RMSSD)ϭ23Ϯ32 versus 51Ϯ48 ms (PϽ0.002); ⌬percentage of successive RR interval differences Ͼ50 ms (⌬pNN50)ϭ5Ϯ15% versus 14Ϯ12% (PϽ0.05); and ⌬HF normalized powerϭϪ2Ϯ7 versus 9Ϯ8 normalized units (PϽ0.01), 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): ⌬RMSSDϭϪ8Ϯ8 versus Ϫ24Ϯ15 ms (PϽ0.001); ⌬pNN50ϭϪ6Ϯ11% versus Ϫ15Ϯ19% (PϽ0.01); ⌬HF normalized powerϭϪ7Ϯ13 versus Ϫ13Ϯ11 normalized units (PϽ0.05), respectively. The change in cross-spectral ␣-index calculated as the square root of the ratio of RR interval power to systolic spectral power in the HF band (although not ␣-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 (⌬ϭ4Ϯ8 versus 14Ϯ15 ms/mm Hg, respectively; PϽ0.02) and with sodium nitroprusside compared with hydralazine (⌬ϭϪ7Ϯ6 and Ϫ9Ϯ7 ms/mm Hg, respectively; PϽ0.05). In conclusion, these data demonstrate that NO augments cardiac vagal control in humans. Key Words: nitric oxide Ⅲ heart rate Ⅲ baroreceptors Ⅲ autonomic nervous system Ⅲ blood pressure T he powerful influence of autonomic control on the natural history of cardiac disease is evidenced by large trials showing that reduced heart rate variability (HRV) and baroreflex sensitivity (BRS) are independent indicators of adverse prognosis. 1,2 However, the mechanisms controlling cardiovascular autonomic function remain poorly defined.The initial suggestion that nitric oxide (NO) may be an important mediator in cardiac autonomic control came from the demonstration of discrete neuronal populations that possess NO synthase at numerous sites within known cardiac autonomic pathways. 3 Animal evidence suggests that the NO synthesized at these sites is active in modulating activity within both limbs of the autonomic nervous system. NO appears to act as a sympatholytic agent, decreasing activity within sympathoexcitatory brain stem nuclei and reducing central ...

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The finding of no difference in insulin sensitivity between the two groups contrasts with, but does not entirely contradict, the results of previous epidemiological studies--perhaps suggesting that longer term changes such as liver enzyme induction may be important. The difference in insulin secretion questions the validity of previous studies of the influence of alcohol on insulin sensitivity, where insulin levels were used as a surrogate for insulin resistance.

1. We have previously shown that brief voluntary isometric contractions of upper arm flexor muscles performed for one respiratory cycle elicit a significant decrease in the R-R interval. The present study was designed to determine if similar changes are produced by non-voluntary electrically evoked contractions and, if so, to establish the consistency and repeatability of the associated changes in the R-R interval. 2. The heart rate (R-R interval) response to voluntary or non-voluntary brief isometric contraction equivalent to 40% of the maximum voluntary contraction was studied in 10 healthy young male subjects during controlled ventilation at supine rest. 3. The absolute values of R-R intervals occurring in any one of 10 arbitrary phases of a respiratory cycle were measured and plotted by a computer. 4. Both voluntary and non-voluntary contractions elicited similar changes in heart rate and R-R interval, which were greater during expiration than during inspiration. 5. This confirms our previous finding that the magnitude of the R-R interval changes, with brief isometric contraction, is positively related to the degree of cardiac vagal tone. 6. Analysis of the variability between repeated tests initiated in either inspiration or expiration revealed that there was significantly less variability with the electrically induced contraction. 7. It was concluded that electrically induced contractions of 40% maximal voluntary contraction are a viable alternative to voluntary contractions and provide a more controllable means of measuring cardiac vagal withdrawal.