A study of the renin inhibitor H142 in man.
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 per h for 30 min while supine and thereafter with dextrose for 1 1/2 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 the H142 infusion was stopped. In contrast, total renin concentration as measured by radio-immunoassay rose while ANG I and II fell, subsiding when 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 a modest but significant increase in the heart rate. These studies confirm H142 as an effective inhibitor of human renin in vivo.
D000328:Adult; D000808:Angiotensinogen / Q000008:administration & dosage / Q000031:analogs & derivatives; D000809:Angiotensins; D001794:Blood Pressure / Q000187:drug effects*; D004039:Diet, Sodium-Restricted; D004837:Epinephrine / Q000097:blood; D005665:Furosemide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D009638:Norepinephrine / Q000097:blood; D005082:Physical Exertion; D011187:Posture; D012083:Renin / Q000097:blood*; D012964:Sodium / Q000652:urine; D000092502:Renin Inhibitors
D000808:Angiotensinogen; D000809:Angiotensins; D004837:Epinephrine; D005665:Furosemide; D009638:Norepinephrine; D012083:Renin; D012964:Sodium; D000092502:Renin Inhibitors; C039583:H 142