Power spectrum analysis of heart rate fluctuations provides a quantitative noninvasive means of assessing the functioning of the short-term cardiovascular control systems. We show that sympathetic and parasympathetic nervous activity make frequency-specific contributions to the heart rate power spectrum, and that renin-angiotensin system activity strongly modulates the amplitude of the spectral peak located at 0.04 hertz. Our data therefore provide evidence that the renin-angiotensin system plays a significant role in short-term cardiovascular control in the time scale of seconds to minutes.

Spectral analysis of spontaneous heart rate fluctuations were assessed by use of autonomic blocking agents and changes in posture. Low-frequency fluctuations (below 0.12 Hz) in the supine position are mediated entirely by the parasympathetic nervous system. On standing, the low-frequency fluctuations increase and are jointly mediated by the sympathetic and parasympathetic nervous systems. High-frequency fluctuations, at the respiratory frequency, are decreased by standing and are mediated solely by the parasympathetic system. Heart rate spectral analysis is a powerful noninvasive tool for quantifying autonomic nervous system activity.

It has long been recognized that the instantaneous heart rate, arterial blood pressure, and other hemodynamic parameters fluctuate on a beat-to-beat ba-

We investigated the hypothesis that beat-to-beat variability in hemodynamic parameters reflects the dynamic interplay between ongoing perturbations to circulatory function and the compensatory response of short-term cardiovascular control systems. Spontaneous fluctuations in heart rate (HR), arterial blood pressure, and respiration were analyzed by spectral analysis in the 0.02- to 1-Hz frequency range. A simple closed-loop model of short-term cardiovascular control was proposed and evaluated in a series of experiments: pharmacological blockades of the parasympathetic, alpha-sympathetic, beta-sympathetic, and renin-angiotensin systems were used to open the principal control loops in order to examine changes in the spectral pattern of the fluctuations. Atrial pacing was used to examine blood pressure variability in the absence of HR variability. We found that respiratory frequency fluctuations in HR are parasympathetically mediated and that blood pressure fluctuations at this frequency result almost entirely from the direct effect of centrally mediated HR fluctuations. The sympathetic nervous system appears to be too sluggish to mediate respiratory frequency variations. Low-frequency (0.02-0.09 Hz) fluctuations in HR are jointly mediated by the parasympathetic and beta-sympathetic systems and appear to compensate for blood pressure fluctuations at this frequency. Low-frequency blood pressure fluctuations are probably due to variability in vasomotor activity which is normally damped by renin-angiotensin system activity. Blockade of the alpha-adrenergic system, however, does not significantly alter low-frequency blood pressure fluctuations.

We postulated that measurements of autonomically mediated fluctuations in heart rate might provide a quantitative probe of biological aging. We used power spectrum analysis of instantaneous heart rate while 33 male subjects matched their breathing to a metronome at 15 breaths/min. Measurements were made in supine and standing position. Total power and its two major components, high- and low-frequency power, declined with age in both positions but at different rates. High-frequency power that represents parasympathetically mediated respiratory sinus arrhythmia declined linearly in supine position only in subjects 9-28 yr with a slope of -0.796, which was significantly different from zero at P = 0.0007. The absolute value of high-frequency power in standing position was approximately 60% of that in supine, a difference that was statistically significant (P = 0.01). Low-frequency power that represents beta-adrenergically mediated heart rate fluctuations, especially in standing position, declined linearly to 62 yr of age (P = 0.0001). Mean heart rate increased 17.2 beats/min, and diastolic blood pressure increased 8 mmHg in the entire group in the standing compared with supine position. There were no significant differences in these changes above and below 30 yr of age. We conclude that the influence of the two major mechanisms that modulate heart rate decline at significantly different rates with aging.