THE EFFECT OF VALSARTAN ON THE ANGIOTENSIN-II PRESSOR-RESPONSE IN HEALTHY NORMOTENSIVE MALE-SUBJECTS

Objective: Valsartan is an oral antagonist of angiotensin II that comp etes with angiotensin LI for the AT(1)-receptor and is being developed as an antihypertensive agent. This study assessed the ability of 80 m g valsartan to inhibit the pressor effect of exogenous angiotensin II in healthy normotensive men, fist after a single dose and then after m ultiple doses once daily for 7 days. Methods: This was a single-center , double-blind, placebo-controlled, randomized crossover study. Six he althy men underwent angiotensin II challenges to determine a suitable dose required to increase their systolic blood pressure by approximate ly 30 mm Hg. Each subject then received an 80 mg dose of valsartan or matching placebo. The inhibition of the angiotensin II presser effect was determined by the systolic blood pressure response to repeated ang iotensin II challenges at multiple time points. Results: Systolic bloo d pressure responses to angiotensin II challenges after single and mul tiple doses of valsartan were significantly lower than placebo, indica ting that valsartan blocked the blood pressure response to angiotensin II. The maximum blocking effect was observed within 2 to 3 hours. Mea n data suggested that differences in effect between valsartan and plac ebo were similar after both single and multiple doses and persisted up to 24 hours after administration. The angiotensin II blocking effect was maintained up to this time, despite low plasma valsartan levels an d minimal accumulation after multiple doses. Conclusion: Valsartan, 80 mg, is a potent angiotensin II antagonist with a rapid onset of actio n and persistent angiotensin II inhibition up to 24 hours. There is no attenuation of this effect after multiple doses.