Systemic and renal hemodynamic effects of the AT1 receptor antagonist, ZD 7155, and the AT2 receptor antagonist, PD 123319, in conscious lambs

Abstract

Experiments were carried out to investigate age- and dose-dependent effects of the selective AT(1) receptor antagonist, ZD 7155, and the selective AT(2) receptor antagonist, PD 123319, on systemic and renal hemodynamics in conscious, chronically instrumented lambs aged approximately 1 and approximately 6 weeks of postnatal life. Mean arterial pressure (MAP), mean venous pressure (MVP), and renal blood flow (RBF) were measured for 10 min before and for 120 min after ZD 7155, PD 123319, or vehicle. In both age groups, administration of ZD 7155 decreased renal vascular resistance (RVR) and increased RBF within 5 min. These responses lasted less than 90 min but were not dose-dependent. MAP decreased by 30 min after administration of ZD 7155 in both age groups at doses >/=400 microg kg(-1); the remaining decreased for up to 120 min, depending upon the dose. Pressor responses to angiotensin II (ANG II) were abolished within 5 min of administration of all doses of ZD 7155, at both 1- and 6 weeks. PD 123319 had no detectable effects on systemic or renal hemodynamics or on the pressor responses to ANG II. Therefore, under physiological conditions in conscious newborn animals, ANG II modulates both resting blood pressure and RVR through activation of AT(1) but not AT(2) receptors.