Plasma Angiotensins, Renin, and Blood Pressure During Acute Renin Inhibition by CGP 38 560A in Hypertensive Patients

Abstract

The new renin inhibitor CGP 38560A has been shown to block angiotensin (ANG) production in healthy volunteers. In order to determine its potential antihypertensive effect, the compound was administered in a 30-min infusion, in 12 hypertensive patients (mean blood pressure (BP): 112.8 ± 3.5 mm Hg). These patients were selected for their sensitivity to Captopril: a single oral dose of 50 mg Captopril lowered their mean BP by 8.8 ± 2.2 mm Hg after 30 min and by 15.3 ± 1.5 mm Hg after 90 min. At the end of the renin inhibitor infusion, mean blood pressure decreased by 5.7 ± 2.2 mm Hg in the six patients infused with the dose of 0.125 mg/kg and by 6.0 ± 1.8 mm Hg in the six patients infused with 0.250 mg/kg. The fall in blood pressure was correlated to the initial plasma renin activity (PRA) (r = 0.61, P < .05). A dose-dependent effect was observed on plasma ANG I which fell by 74% with 0.125 mg/kg and by 94% with 0.250 mg/kg. Identical falls were found for plasma ANG II (72% and 94%, respectively) and ANG I and ANG II were well correlated (r = 0.91, P < .001). The fall in BP was correlated to the fall in plasma ANG I (r = 0.77, P < .01). The time-course of the BP changes was parallel to the changes in plasma angiotensins, as were the slightly delayed rise and fall in active renin measured by a direct immunoradiometric assay. When measured by the conventional ANG I radioimmunoassay, PRA values indicated a long-lasting inhibition. The arte- factual nature of the latter result is demonstrated by the different results obtained with an ANG I antibody-trapping radioimmunoassay, which followed more closely plasma ANG I levels. Am J Hypertens 1989; 2:819-827