Clinical and biochemical effects of the renin inhibitor H142 in humans

Journal of Cardiovascular Pharmacology
D J WebbJ Menard

Abstract

The inhibitor of human renin, H142, was studied in nine male volunteers. On three occasions, in random order, volunteers were infused with 5% dextrose, or with H142 at 1.0 or 2.5 mg/kg/h, for 30 min while supine and thereafter with dextrose for 1.5 h. There was a marked reduction in plasma active renin concentration as assayed by an enzyme-kinetic method, with parallel falls in the circulating concentrations of angiotensins (ANG) I and II, all of which rebounded transiently to values above basal after H142 infusion was stopped. In contrast, total renin concentration as measured by radioimmunoassay rose while ANG I and II fell, subsiding after H142 was discontinued. There was a slight but significant increase in plasma noradrenaline as renin became inhibited: plasma adrenaline was unchanged. H142 produced a slight fall in systolic blood pressure (SBP) and a clearer, highly significant, dose-related fall in diastolic blood pressure (DBP). There was modest but significant increase in the heart rate. These studies confirm H142 as an effective inhibitor of human renin in vivo.

Citations

Jan 1, 1990·European Journal of Clinical Pharmacology·L WidmannM Machwirth
Jan 8, 2008·Current Hypertension Reports·Roland E Schmieder
Jan 1, 1994·Pharmacology & Therapeutics·J M WoodJ Maibaum
Jan 16, 2010·Expert Opinion on Drug Metabolism & Toxicology·Subhashis ChakrabortySanjay Singh
May 19, 2010·American Journal of Therapeutics·Zafar H IsrailiValmore Bermúdez
Apr 1, 1990·Medicinal Research Reviews·W J Greenlee

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