Effect of aprotinin-induced kallikrein inhibition on the cardiovascular and renal action of captopril in diuretic-treated dogs.
By using aprotinin, a potent kallikrein inhibitor, the role of kinin formation in the cardiovascular and renal effects of captopril was assessed in pentobarbital-anesthetized dogs previously undergoing hydrochlorothiazide treatment (2.5 mg/kg, p.o., b.i.d.) for 5 days. A fall in mean arterial pressure (MBP) from 117 +/- 8 to 94 +/- 6 mmHg followed i.v. administration of captopril, 1 mg/kg. A concomitant rise in renal blood flow (RBF) from 168 +/- 18 to 205 +/- 20 ml/min occurred without changes in glomerular filtration rate (GFR) and with cardiac output tending to decrease. Urine flow (V) tended to rise while Na+ and K+ excretion were variable. With i.v. infusion of aprotinin (900 KIU/min) the hypotensive response to captopril was unaffected (from 103 +/- 5 to 75 +/- 8 mmHg) suggesting that captopril decreases BP independent of kinin accumulation. However, aprotinin completely abolished the renal vasodilator response to captopril (from 163 +/- 25 to 143 +/- 22 ml/min). In addition, there was a concomitant fall in GFR, V and electrolyte excretion. In comparison, the cardiovascular and renal effects of saralasin (3 micrograms/kg/min, i.v.) were not altered by aprotinin. It is, therefore, concluded that, in dogs with stimulated renin-angiotensin system, the plasma kinins do not contribute to the hypotensive action of captopril but play an important role in inducing renal vasodilatation and supporting kidney function.
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects*; D004232:Diuretics / Q000494:pharmacology*; D004285:Dogs; D004573:Electrolytes / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D011392:Proline / Q000031:analogs & derivatives*; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D012504:Saralasin / Q000494:pharmacology
D004232:Diuretics; D004573:Electrolytes; D007611:Aprotinin; D011392:Proline; D002216:Captopril; D007610:Kallikreins; D012083:Renin; D012504:Saralasin