The hypotensive effect of single-dose captopril in diabetics.
To determine the role of the kallikrein-kinin (KK) system in patients with diabetes mellitus in relation to nephropathy and/or hypertension, the single-dose effects of captopril (25 mg, p.o.) were examined in 9 control subjects and 32 diabetics (group 1; 11 normotensives without nephropathy, group 2;10 hypertensives without nephropathy, group 3; 11 hypertensives with nephropathy). Significant hypotensive effects of captopril were found in groups 1 and 2 as well as in the control group, but not in group 3. These hypotensive effects were completely blocked by the infusion of ethyl-p-(6-guanidinohexanoyloxy) benzoate methanesulfonate (FOY), a kallikrein inhibitor. The administration of captopril during vehicle infusion induced a significant elevation of plasma renin activity (PRA) at 60 and 120 min after captopril in each group, except for group 3. FOY cancelled these captopril-induced effects on PRA in those groups. No correlation was found between pretreatment PRA and the changes in mean blood pressure (MBP) after captopril during vehicle infusion in whole diabetics. In addition, the daily urinary excretion of kallikrein in group 3 was significantly lower than that in groups 1 and 2 as well as in the control group. These results suggest that the hypotensive action of captopril in diabetics without nephropathy may be largely due to activating the KK system, and that the KK system may be suppressed in hypertensive diabetics with nephropathy.
D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage*; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D004341:Drug Evaluation; D016670:Gabexate; D006146:Guanidines; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007610:Kallikreins / Q000652:urine; D012083:Renin / Q000097:blood
D006146:Guanidines; D016670:Gabexate; D002216:Captopril; D007610:Kallikreins; D012083:Renin