A Transition-state Analogue Inhibitor of Human Renin (H.261): Test in vitro and a Comparison with Captopril in the Anaesthetized Baboon


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Abstract

H.261, a new transition state inhibitor of human renin with an IC50 of 6.9 x 10-10 M, was given by intravenous infusion to six anaesthetized baboons. The inhibitor was infused first at 0.1 (µmol/kg/h for 15 min, then at 1.0 µmol/kg/h for a further 15 min. After a recovery period of 2 h in which the animals received 5% dextrose, they were infused with captopril, 25 µmol/kg/h for 15 min. At both rates of infusion H.261 markedly and significantly reduced the enzymatic action of renin in plasma, the blood concentration of angiotensin I, the plasma concentration of angiotensin II and mean arterial pressure. All changes reverted towards or to control values in the subsequent control period. Captopril also lowered plasma angiotensin II concentration and mean arterial pressure markedly and significantly but, as expected for an inhibitor of the angiotensin l-converting enzyme, plasma active renin concentration and blood angiotensin I concentration increased. The changes of angiotensin II and arterial pressure were similar with captopril and H.261

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