Submitted on June 7, 2004
Accepted on October 5, 2004
Feedback Effects of Circulating Norepinephrine on Sympathetic Outflow in Healthy Subjects
Mikko P. Tulppo1*, Heikki V. Huikuri2, Elli Tutungi3, Derek S. Kimmerly3, Adrian W. Gelb3, Richard L. Hughson4, Timo H. Makikallio1, and Kevin J. Shoemaker3
1 Laboratory of physiology, Merikoski Rehabilitation and Research Centre, Oulu, Finland; Department of Medicine, University of Oulu, Oulu, Finland
2 Department of Medicine, University of Oulu, Oulu, Finland
3 School of Kinesiology, University of Western Ontario, London, Canada
4 Applied Health Sciences, University of Waterloo, Waterloo, Canada
* To whom correspondence should be addressed. E-mail: mikko.tulppo{at}merikoski.fi.
The amplitude of low-frequency (LF) oscillations of heart rate (HR) usually reflects the magnitude of sympathetic activity, but during some conditions, e.g. physical exercise, high sympathetic activity results in a paradoxical decrease of LF oscillations of HR. We tested the hypothesis that this phenomenon may result from a feedback inhibition of sympathetic outflow
caused by circulating norepinephrine (NE). A physiological dose of NE (100 ng.kg-1.min-1) was infused into eight healthy subjects, and infusion was continued after alpha-adrenergic blockade (with phentolamine; PHE). Muscle sympathetic nervous activity (MSNA) from the peroneal
nerve, LF (0.04-0.15 Hz) and high frequency (HF; 0.15-0.40 Hz) spectral components of HR variability, and systolic blood pressure variability were analyzed at the baseline, during the NE infusion, and during the NE infusion following PHE administration. The NE infusion increased
the mean blood pressure and decreased the average HR (P<0.01 for both). MSNA (10±2 vs. 2±1 burst/min, P<0.01), LF oscillations of HR (43±13 vs. 35±13 nu, P<0.05), and systolic blood pressure (3.1±23 vs. 2.0±1.1 mmHg2, P<0.05) decreased significantly during the NE infusion. During the NE infusion following PHE, average HR and mean blood pressure returned to the baseline levels. However, MSNA (4±2 burst/min), LF power of HR (33±9, nu), and systolic blood pressure variability (1.7±1.1 mmHg2) remained significantly (P<0.05 for all) below the baseline values. Baroreflex gain did not change significantly during the interventions. Elevated levels of circulating NE cause a feedback inhibition on sympathetic outflow in healthy subjects.
These inhibitory effects do not seem to be mediated by pressor effects on baroreflex loop, but perhaps by a presynaptic autoregulatory feedback mechanism or some other mechanism that is not prevented by a non-selective alpha-adrenergic blockade.
