Pressor Responses to Norepinephrine During Captoprii In Renal Prehypertensive Rabbits

The role of angiotensin II (All) in pressor hyperresponsiveness was examined in conscious one-kidney, one clip rabbits with renal artery stenosis 01 3-days' duration (renal prehypertensive rabbits). Conscious one-kidney rabbits without renal artery stenosis served as controls. Two experiments were performed. The first experiment used four groups of six rabbits each, to examine the pressor responses to intravenous (i.v.) infusions of norepinephrine (NE) at several doses, ranging from 25 to 1200 ng/min/kg body weight, in 3-day renal artery stenosis and in 3-day control rabbits, receiving NE plus the angiotensin-converting enzyme inhibitor, captoprii (SQ 14,225), or receiving NE alone. The arterial pressure and values for plasma renin activity (PRA) were the same in the renal artery stenosis rabbits as in the controls. The exaggerated pressor responses to NE in the renal artery stenosis rabbits were restored to normal by captoprii administration. The second experiment investigated the pressor responses to i.v. infusions of NE at 800 ng/min/kg in six rabbits with renal artery stenosis and in six control rabbits before captoprii, during captoprii administration, and during the administration of captoprii plus the i.v. infusion of AH at 0.5,1.0, and 2.0 ng/min/kg body weight. Plasma concentrations of All were determined at each point in this experiment. The renal artery stenosis rabbits had the same values for arterial pressure and PRA as the control rabbits. The renal artery stenosis rabbits had increased pressor responses to NE, and this pressor hyperresponsiveness was abolished by captoprii. The i.v. infusion of All during captoprii treatment in the renal artery stenosis rabbits increased the pressor responses to NE, and All infusion at 2.0 ng/min/kg completely restored the pressor hyperresponsiveness in these rabbits. The control rabbits had no changes in the pressor responses to NE with captoprii or with captoprii plus any of the AH doses. Before captoprii, the control and renal artery stenosis rabbits had the same plasma concentrations of AH. With captoprii, plasma concentrations of All in the renal artery stenosis rabbits decreased to undetectably low levels and remained so during the infusions of AH at all doses. This study provided strong evidence that plasma All plays an important role in the enhanced pressor responses to NE in 3-day renal artery stenosis rabbits, and that this effect is not due to elevated plasma levels of AH. (Hypertension 5: 159-165, 1983)