PD123319 an angiotensin II (An) -2 blocker: A potent regulator of vena ça VA pressure and flow in the rabbit

A role for A_II (and its blockers) in regulation of aortic and vena cava dynamics during exercise has been proposed. Using anesthetized rabbits (n=6) in which aortic and vena cava pressure and flow were measured (infra renal) the effects of A_II (0.2 μg/kg) delivered into the thoracic aorta was examined before and after blockade with losarten, an A_II-1 blocker (1 mg/kg) and following graded doses of PD123319 (0.2 >(g/kg to 15 mg/kg) an A_II-2 blocker. A_II induced a consistent arterial pressor response. Venous responses were delayed. Analysis of net change of venous volume suggested that AH caused a decrease. Losarten caused no hemodynamic changes. Losarten blocked all effects of AH- PD123319 in low doses 2mg/kg) caused a minimal increase in arterial pressure (diastolic) with a decrease in venous pressure. Venous flow increased. At higher doses (> 2 mg/kg) a biphasic arterial pressure response was observed, initially a fall followed by return to control, diastolic pressures usually increased. Venous pressure increased in a dose response fashion with vena cava spasm being observed at higher doses. PD 123319 decreased venous volume similar to A_II. The hemodynamic response to A_II given following PD 123319 was little changed. Subsequent doses of PD 123319 were less effective. These data suggest a role for A_II in control of venous return. PD 123319 at low doses has A_II like properties in the rabbit venous circulation with much less of A_II's arterial constrictor properties.