Chronic angiotensin II infusion but not bradykinin blockade abolishes the antiproteinuric response to angiotensin-converting enzyme inhibition in established adriamycin nephrosis

Angiotensin-converting enzyme (ACE) inhibition reduces proteinuria in estab lished adriamycin nephrosis. To investigate whether the reduction in protei nuria is due to decreased generation of angiotensin II (AngII) or to decrea sed degradation of bradykinin, four series of experiments in established ad riamycin nephrosis were performed. In the first series, 2 mg/kg lisinopril reduced BP from 117 +/- 4 to 67 +/- 2 mmHg and proteinuria from 335 +/- 66 to 57 +/- 10 mg/24 h after 2 wk of treatment. Subsequent continuous intrape ritoneal infusion of AngII: (250 ng/kg per min) for 2 wk partially restored proteinuria to 180 +/- 42 mg/24 h, whereas BP increased to 97 +/- 3 mmHg. Subsequent withdrawal of AngII restored the antiproteinuric effects of lisi nopril, whereas subsequent withdrawal of lisinopril restored proteinuria to pretreatment values. In the second series, AT1 receptor blockade induced a fall in BP and proteinuria similar to that by lisinopril. In the third ser ies, lisinopril reduced BP from 121 +/- 5 to 68 +/- 2 mmHg and proteinuria from 355 +/- 90 to 101 +/- 10 mg/24 h. Subsequent intraperitoneal infusion of bradykinin antagonist (HOE 140; 1 mg/kg per 24 h) for 2 wk did not affec t BP (72 +/- 2 mmHg) or proteinuria (92 +/- 15 mg/24 h). In the fourth seri es, bradykinin (3 mg/kg per 24 h) was infused for 2 wk to mimic decreased b radykinin breakdown. This did not affect proteinuria, but induced a fall in BP from 114 +/- 3 to 93 +/- 4 mmHg. The BP-lowering effect of exogenous br adykinin was completely reversed by 1 wk infusion of HOE 140 (93 +/- 4 to 1 13 +/- 4 mmHg), while proteinuria remained unchanged. In conclusion, the an tiproteinuric effect of ACE inhibition appears to be independent of bradyki nin in this model, supporting a main role for reduction of AngII in the ant iproteinuric action of ACE inhibition.