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Objective: It is known that the angiotensin II AT1 receptor antagonists block the renin angiotensin system and result in consequent increases in plasma renin levels by interfering with feedback. Further, it has previously been documented that irbesartan (IRB) and candesartan cilexetil (CAN) exhibit a longer duration of angiotensin II (ANG II) antagonism than do losartan and valsartan (Malerczyk C et al.: Br J Clin Pharmacol 1998;45:567–573; Belz GG et al.: Clin Pharmacol Ther 1999;66:367–373). We evaluated data from a direct comparison of the ANG II antagonistic effects of IRB and CAN to evaluate their effects on stimulating plasma renin levels. Methods: Eighteen healthy males were enrolled in a doubleblind, randomized, cross-over study and received IRB 150 mg and CAN 8 mg for one week each. Plasma renin activity at rest and the rightward shift (measured as dose-ratio [DR1]) of blood pressure response curves to exogenous ANG II were used to assess the ANG II antagonism in vivo. The degree of receptor occupation in plasma ex vivo was determined by radioligand rat lung receptor assay (RRA). Results: Both IRB and CAN shifted ANG II dose effect curves rightward to a similar degree (max ;35-fold) and yielded mean DR-1s of .1 for approximately 48 hours, indicating strong and long lasting ANG II antagonism. The antagonistic activity in plasma as measured by RRA was distinctly higher (p , 0.01) following administration of IRB. Plasma renin activity during the periods with high antagonistic activity was significantly higher following IRB (p 5 0.02) in absolute terms (left figure) and when related to the ANG II antagonistic effect (right figure).

american journal of hypertension

Irbesartan results in more complete blockade of human renal at1-receptor mediated effects than does candesartan cilexetil as evidenced by higher plasma renin levels