Responses of the kallikrein-kinin system to angiotensin converting enzyme inhibitors in the rat.
Three structurally different drugs, MK421, SA446 and captopril, are angiotensin converting enzyme inhibitors. They induced a significantly greater fall in systolic blood pressure in sodium depleted rats than in sodium repleted ones. The combined administration of vasopressin or norepinephrine with MK421 eliminated the hypertensive effect of vasopressin or norepinephrine. Urinary kallikrein and kinin excretion were increased by MK421, SA446 or captopril in the sodium depleted rats whereas any significant changes in them were not observed in the sodium repleted rats. The combined administration of norepinephrine with MK421 induced further increases in urinary kallikrein and kinin excretion when compared to rats infused with norepinephrine alone, whereas the combined administration of vasopressin with MK421 did not induce any changes in them when compared to rats infused with vasopressin alone. Chronic infusion of captopril for up to 6 days in the rats induced a reduction of the vascular response to exogenous bradykinin; the blood pressure fall was less than that of the controls by 17% on Day 2 and by 18% on Day 6. These results indicate that the hypotensive response to angiotensin converting enzyme inhibitors was in part associated with the enhanced renal and vascular smooth muscle kallikrein-kinin system.
D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D004039:Diet, Sodium-Restricted; D004151:Dipeptides / Q000494:pharmacology*; D004656:Enalapril; D007610:Kallikreins / Q000502:physiology / Q000652:urine*; D007705:Kinins / Q000502:physiology / Q000652:urine*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000008:administration & dosage; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System; D013438:Sulfhydryl Compounds; D053778:Thiazolidines; D014667:Vasopressins / Q000008:administration & dosage
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D007705:Kinins; D013438:Sulfhydryl Compounds; D053778:Thiazolidines; D014667:Vasopressins; D004656:Enalapril; D011392:Proline; D002216:Captopril; D015097:3-Mercaptopropionic Acid; C033437:rentiapril; D007610:Kallikreins; D001920:Bradykinin; D009638:Norepinephrine