Hormonal and Renal Responses to Oral Once-Daily Calcium Entry Blocker in Normotensive and Hypertensive Persons

Abstract

A newly produced calcium entry blocker, KW3049 (Kyowa Hakko, Tokyo, Japan), which maintains its antihypertensive action for >24 h, was administered orally once daily to 12 subjects (5 normotensive, 7 hypertensive) for 12 days. To elucidate its hypotensive efficacy and mechanisms of action, daily changes in blood pressure and heart rate, serial alterations in the renin-angiotensin system and sympathetic nervous system, and the renal hemodynamics were investigated. KW3049 caused a significant decrease in mean arterial pressure from 124 + 3 to 107 + 2 mm Hg, accompanied by a moderate increase in heart rate (+ 15%). The urine volume and urinary excretion of sodium were persistently increased in hypertensive subjects with improvement of the renal blood flow. The plasma renin activity and plasma and urinary norepinephrine (NE) increased significantly (p < 0.05) on the sixth day and returned to baseline levels on the twelfth day. In addition to these renal and hormonal changes, the pressor responses to infused NE and angiotensin II were attenuated on the twelfth day after KW3049 administration. The above findings suggest that only once-daily administration of KW3049 is able to reduce the blood pressure without fluctuation, and its antihypertensive mechanisms are related to a natriuretic action and attenuation of pressor responses as well as to strong vasodilation.