Morning sympathetic nerve activity is not increased in humans. Implications for mechanisms underlying the circadian pattern of cardiac risk.

Abstract

The sympathetic nervous system has been implicated in the circadian pattern of myocardial infarction and sudden death. It has been postulated that sympathetic nerve activity is higher in the morning than at other times of the day and that this increase reflects an endogenous circadian pattern or is triggered by changes in posture and the onset of morning activities. To test these two concepts, we made microneurographic recordings of muscle sympathetic nerve activity in the morning (6:30 to 8:30 AM) and afternoon (2:00 to 4:00 PM) in eight healthy subjects (mean age, 42 +/- 4 years), and intraindividual comparisons (paired t tests) were made during (1) supine rest, (2) postural changes simulated by lower body negative pressure (LBNP), and (3) activity produced by sustained handgrip. Plasma cortisol, known to follow a circadian pattern, was measured to assess whether normal circadian patterns were present under experimental conditions. Plasma cortisol exhibited a robust circadian variability (plasma cortisol [mean +/- SEM], AM versus PM: 17 +/- 1 versus 9 +/- 1 microgram/dL, P = .008). In contrast, basal muscle sympathetic nerve activity was not higher in the morning compared with the afternoon (group mean sympathetic nerve activity, AM versus PM: 38 +/- 6 versus 38 +/- 6 bursts per minute, P = NS). Similarly, plasma norepinephrine levels were not higher in the morning compared with the afternoon (plasma norepinephrine, AM versus PM: 157 +/- 17 versus 173 +/- 14 pg/mL, P = NS). During postural stress simulated by LBNP, the magnitude of change in sympathetic nerve activity was not higher in the morning compared with the afternoon (LBNP -20 mm Hg, AM versus PM: 103 +/- 34% versus 157 +/- 31%, P = NS). Finally, the magnitude of change in muscle sympathetic nerve activity during the first minute of handgrip exercise (AM versus PM: 11 +/- 17% versus 8 +/- 11%, P = NS) or the second minute of handgrip exercise (AM versus PM: 59 +/- 34% versus 60 +/- 15%, P = NS) was not higher in the morning compared with the afternoon. These findings challenge the concept that sympathetic nerve activity is higher in the morning either during supine rest or during postural changes and activity. We speculate that if the sympathetic nervous system is involved in the circadian pattern of sudden death, this involvement must reflect exaggerated morning end-organ responsiveness to norepinephrine, not enhanced morning sympathetic outflow.