Role of cardiac factors in the initial hypotensive action by beta-adrenoreceptor blocking agents.

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Abstract
The blood pressure decrease after .beta.-blockade is delayed and there are little data on the hemodynamic events associated with the initial decrease in blood pressure. The present study measured the hemodynamics of the initial hypotensive action of timolol maleate, a nonselective .beta.-adrenoreceptor blocking agent, in 10 patients with essential hypertension. Frequent measurements were made for the 1st 30 h of treatment, and follow-up measurements made at 3 and 6 wk. Before treatment, mean arterial blood pressure, cardiac output and arteriovenous O2 difference were 115.9 .+-. 9.1 mm Hg, 4.65 .+-. 1.05 l/min, and 55.0 .+-. 9.6 ml/l, respectively. At 3 h after the 1st dose of timolol, blood pressure had fallen 13.5 .+-. 8.2 mm Hg (P < 0.05). This was preceded by an initial decrease in cardiac output, which was not associated with a simultaneous decrease in blood pressure, and by an increase of arteriovenous O2 difference. The early, statistically significant, decrease in cardiac output was followed by a return to normal output, which coincided with the onset of blood pressure reduction. The magnitude of the initial decrease of cardiac output and of the initial increase in arteriovenous O2 difference was significantly correlated to the later decrease in blood pressure (7 h after 1st dose). These hemodynamic observations are consistent with the notion that early underperfusions of tissue play a role in the initial hypotensive action of .beta.-blockers. After 6 wk, the blood pressure remained lower but the cardiac output was again decreased at that point. As with many antihypertensive agents, there was a difference between the early and late hemodynamic pattern. Only the early pattern was consistent with a peripheral adjustment of circulation to the decreased cardiac output. The early responders tended to remain responsive in the later phase. It is speculated that the initial response is important and sets into motion some secondary adjustments that later alter the hemodynamic picture.