We evaluated a method of baroreflex testing involving sequential intravenous bolus injections of nitroprusside followed by phenylephrine and phenylephrine followed by nitroprusside in 18 healthy men and women, and we drew inferences regarding human sympathetic and vagal baroreflex mechanisms. We recorded the electrocardiogram, photoplethysmographic finger arterial pressure, and peroneal nerve muscle sympathetic activity. We then contrasted least squares linear regression slopes derived from the depressor (nitroprusside) and pressor (phenylephrine) phases with 1) slopes derived from spontaneous fluctuations of systolic arterial pressures and R-R intervals, and 2) baroreflex gain derived from cross-spectral analyses of systolic pressures and R-R intervals. We calculated sympathetic baroreflex gain from integrated muscle sympathetic nerve activity and diastolic pressures. We found that vagal baroreflex slopes are less when arterial pressures are falling than when they are rising and that this hysteresis exists over pressure ranges both below and above baseline levels. Although pharmacological and spontaneous vagal baroreflex responses correlate closely, pharmacological baroreflex slopes tend to be lower than those derived from spontaneous fluctuations. Sympathetic baroreflex slopes are similar when arterial pressure is falling and rising; however, small pressure elevations above baseline silence sympathetic motoneurons. Vagal, but not sympathetic baroreflex gains vary inversely with subjects’ ages and their baseline arterial pressures. There is no correlation between sympathetic and vagal baroreflex gains. We recommend repeated sequential nitroprusside followed by phenylephrine doses as a simple, efficientmeans to provoke and characterize human vagal and sympathetic baroreflex responses.

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Abstract-Baroreflex sensitivity (BRS) by the spontaneous sequence technique has been widely used as a cardiac autonomic index for a variety of pathological conditions. However, little information is available on determinants of the variability of spontaneous BRS and on age-related reference values of this measurement in a healthy population. We evaluated BRS as the slope of spontaneous changes in systolic blood pressure (BP) and pulse interval from 10 minutes BP (Finapres) and ECG recordings in 1134 healthy volunteers 18 to 60 years of age. Measurement of BRS could be obtained in 90% of subjects. Those with unmeasurable spontaneous BRS had a slightly lower heart rate but were otherwise not different from the rest of the population. BRS was inversely related to age (lnBRS, 3.24Ϫ0.03ϫage; r 2 ϭ0.23; PϽ0.0001) in both genders. In addition, univariate analysis revealed a significant inverse correlation between BRS and heart rate, body mass index, and BP. Sedentary lifestyle and regular alcohol consumption were also associated with lower BRS. However, only age, heart rate, systolic and diastolic BP, body mass index, smoking, and gender were independent predictors of BRS in a multivariate model, accounting for 47% of the variance of BRS. The present study provides reference values for spontaneous BRS in a healthy white population. Only approximately half of the variability of BRS could be explained by anthropometric variables and common risk factors, which suggests that a significant proportion of interindividual differences may reflect genetic heterogeneity. which measures BRS as the slope of the relationship between the increase in systolic blood pressure (SBP) that follows an intravenous bolus of phenylephrine and the reflex lengthening of the pulse interval (PI). By use of this technique, studies have shown BRS to decrease with age 2,3 and in the presence of hypertension, coronary artery disease, and heart failure. 4,5 In addition, a recent large prospective study has demonstrated that BRS is an important independent prognostic predictor of total cardiac mortality in patients after myocardial infarction. 6 In the past few years, noninvasive techniques have gained increasing popularity. In particular, measurement of BRS as the slope of the relationship between spontaneous changes in SBP and PI (the "spontaneous sequence method") 7,8 has proved to be an easy and practical method that minimizes risk and circumvents the problems related to potential extravascular effects of vasoactive agents. 9 However, this technique has been used to date only in small studies. Little information is available regarding determinants of variability of spontaneous BRS in healthy subjects and the feasibility of this measurement in large-scale population studies. In the present study, we evaluated BRS by the spontaneous sequence method in a large population of healthy working subjects between 18 and 60 years of age with the aim of assessing (1) feasibility of this method in a large "field" study; (2) age-adjusted normal ranges for spontan...