Angiotensin II-induced drinking and pressor responses to central or systemic irbesartan and losartan

Angiotensin II (ANG II) is a peptide hormone that is important for maintaining blood pressure and body fluid homeostasis. Two nonpeptide angiotensin type 1 (AT(1)) receptor antagonists, irbesartan and losartan, were compared for their antidipsogenic and antihypertensive efficacy in both normotensive and hypertensive rats. ANG II-induced drinking and pressor responses were examined following central or systemic administration of irbesartan and losartan. Both agents inhibited the drinking response to ANG II in normotensive rats. Irbesartan was more effective than losartan at inhibiting pressor responses to ANG II in normotensive and hypertensive rats. These data indicate that centrally administered irbesartan may be somewhat more effective as an AT(1) receptor antagonist than losartan. However, evaluating the antihypertensive efficacy of these drugs when administered systemically is complex due to several pharmacokinetic factors (e.g., metabolism and lipophilicity).