Circadian Variation in Vascular Tone and Its Relation to α-Sympathetic Vasoconstrictor Activity

BACKGROUND: The frequency of several cardiovascular events, such as myocardial infarction, sudden death, and stroke, is increased during the early morning hours. There is also a similar circadian pattern in several physiologic variables, including blood pressure, suggesting that certain dynamic processes may contribute to the circadian distribution and onset of acute events. METHODS: To determine whether there are circadian variations in vascular tone and to investigate their underlying mechanisms, we measured blood flow and vascular resistance in the forearm and their responses to phentolamine (an alpha-adrenergic-antagonist drug) and sodium nitroprusside (a direct vasodilator) in 12 normal subjects (7 men and 5 women; mean age +/- SD, 44 +/- 9 years) at three different times of day (7 a.m., 2. p.m., and 9 p.m.). The drugs were infused into the brachial artery, and the responses were measured by strain-gauge plethysmography. RESULTS: The basal forearm vascular resistance was significantly higher, and the blood flow significantly lower, in the morning than in the afternoon and evening (mean vascular resistance, 31 +/- 8, 25 +/- 6, and 22 +/- 7 mm Hg per milliliter per minute per 100 ml of forearm volume, respectively; P less than 0.01). The vasodilator effect of phentolamine was also significantly greater in the morning (mean decrease in vascular resistance, 38 +/- 6 percent) than in the afternoon (26 +/- 6 percent) and evening (21 +/- 7 percent) (P less than 0.05). Consequently, there was no circadian variation in vascular resistance or blood flow after the infusion of this drug. In contrast, the vasodilation in response to sodium nitroprusside was similar at all three times of day. CONCLUSIONS: There is a circadian rhythm in basal vascular tone, due either partly or entirely to increased alpha-sympathetic vasoconstrictor activity during the morning. This variation may contribute to higher blood pressure and the increased incidence of cardiovascular events at this time of day.