DISPARITY BETWEEN BLOOD-PRESSURE AND PRA INHIBITION AFTER ADMINISTRATION OF A RENIN INHIBITOR TO ANESTHETIZED DOGS - METHODOLOGICAL CONSIDERATIONS

A dissociation between changes in blood pressure (BP) and plasma renin activity (PRA) has been noted after administration of renin inhibitor s. In the present study, the renin inhibitor PD 132002 was given to sa lt-deplete, anesthetized dogs. PRA was measured at pH 6.0 by a convent ional angiotensin I (ANG I) RIA method (PRA-C) and by an ANG I antibod y-trapping RIA method (PRA-AT) performed at pH 7.4. PD 132002 at 0.01, 0.1, 1, and 10 mg/kg IV, reduced BP by 3 +/- 2, 9 +/- 2, 24 +/- 4, an d 39 +/- 4 mm Hg, respectively, (baseline of 136 +/- 8 mm Hg, N = 5), when infused IV over 30 minutes with a 30 minute recovery between dose s. The BP response at 10 mg/kg equaled that of saralasin (20 ug/kg/min IV). PRA-AT (baseline of 20 +/- 6 ng ANG I/ml/hr, N = 4) was inhibite d by 0%, 28% +/- 12%, 75% +/- 10%, and 97% +/- 1% at 0.01, 0.1, 1, and 10 mg/kg, respectively. Plasma concentrations of immunoreactive ANG I I were also reduced dose-dependently and paralleled changes in BP. In contrast, PRA-C (baseline of 13 +/- 4 ng ANG I/ml/hr, N = 4) was inhib ited by 82% +/- 8% at 0.01 mg/kg and by >98% at higher doses. After a single dose of PD 1 32002 at 10 mg/kg infused over 30 minutes, BP reco very paralleled changes in immunoreactive ANG II and PRA-AT, yet PRA-C inhibition showed no recovery over the same time course. Our data sup port the conclusion that BP relates better to PRA-AT than PRA-C. Thus the dissociation sometimes observed in studies with renin inhibitors b etween changes in BP and PRA may be attributed to the assay used to de termine PRA.