Effect of aprotinin-induced kallikrein inhibition on the cardiovascular and renal action of captopril in diuretic-treated dogs
Vemulapalli, S.; Chiu, P.J.
Archives Internationales de Pharmacodynamie et de Therapie 262(1): 109-123
1983
ISSN/ISBN: 0003-9780 PMID: 6191727 Document Number: 205839
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.