Effect on resting blood pressure and blood pressure homeostasis of short-term administration of the alpha1-adrenergic receptor antagonist, trimazosin, in hypertension

The effects of trimazosin on blood pressure and cardiovascular homeostasis were studied in 12 subjects with untreated essential hypertension of mild or moderate degree. After a 3-day placebo period, the subjects were given trimazosin at the dose of 50, 100, or 200 mg twice daily (7 am and 7 pm) according to a randomized, double-blind crossover protocol. Each treatment was prolonged for 3 days and separated from the subsequent treatment by a 2-day placebo period. Blood pressure (sphygmomanometery) and heart rate were measured at rest during various laboratory maneuvers on the first and third day of the initial placebo, on the first and third day of the drug periods, and on the second day of the intervening placebo periods. Compared to placebo values, trimazosin caused a reduction in systolic and diastolic blood pressure which was well sustained through the time between the morning and the evening administration of the drug and was accompanied by only a slight tachycardia. The antihypertensive effect was similar in the supine and up-right position and in both instances it was greater for the 100 or 200 mg twice daily dose than for the 50-mg twice daily dose. The pressor and tachycardic responses to cold pressor test and to isometric and dynamic exercise were unaffected by the various doses of trimazosin whose antihypertensive effect was therefore similarly evident at rest and during behaviorally occurring blood pressure rises. Trimazosin also left unchanged the blood pressure and heart rate adjustments to passive tilting, its only effect being a modest and asymptomatic reduction in systolic blood pressure when tilting was performed during the first day of its administration at the highest dose. It is concluded that 100 mg or 200 mg twice daily of trimazosin effectively reduced high blood pressure. Both initially and at a later stage these doses did not modify the blood pressure adjustment to tilting, thereby preserving blood pressure homeostasis.