PERSISTENT INHIBITION OF THE PRESSOR AND ALDOSTERONE RESPONSES TO ANGIOTENSIN-II BY TCV-116 IN NORMOTENSIVE SUBJECTS

TCV-116 is an orally active, nonpeptide antagonist of angiotensin-II t ype-1 receptor. The angiotensin-II antagonistic potency of TCV-116 was evaluated in normal volunteers. TCV-116 was administered at single do ses of 1, 2.5, and 5 mg orally on separated days. Before, and 4, 8, an d 24 h after the drug administration, angiotensin-II was infused intra venously at the rate of 2.5 to 40 ng/kg/min for 5 min each. At 2.5 mg of TCV-116, the presser response to angiotensin-II was significantly s uppressed at 4 and 8 hours after drug administration. TCV-116 at 5 mg produced a reduction of basal blood pressure and a suppression of pres ser response to angiotensin-II, which persisted for 24 h. Aldosterone response to exogenous angiotensin-II was suppressed to 10% at 8 h afte r 5 mg of TCV-116 administration and remained suppressed to 48% until 24 h. These results suggest that TCV-116 is a highly potent and long-l asting antagonist of angiotensin-II receptor in man. The renin-angiote nsin system may play a role in the regulation of blood pressure even i n normotensive subjects.