COMBINED EFFECTS OF AN ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR AND A CALCIUM-ANTAGONIST ON RENAL INJURY

Background Angiotensin converting enzyme inhibitors have uniformly bee n shown to prevent the development both of proteinuria and of glomerul osclerosis in rats with a remnant kidney, Conversely, dihydropyridine calcium antagonists (DCA) have failed to demonstrate such a benefit in spite of causing an equivalent reduction in blood pressure, Objective To test the hypothesis that concomitant administration of an angioten sin converting enzyme inhibitor and a DCA would lead to a smaller incr ease both in proteinuria and in glomerulosclerosis relative to that ca used by administration of a DCA alone at similar levels of blood press ure. Methods Experiments were carried out using Sprague-Dawley rats th at had been subjected to five-sixths renal ablation. Animals were allo cated randomly to one of four groups: control (no treatment), amlodipi ne (A rats), benazepril (B rats), or a combination of benazepril and a mlodipine (B + A rats). We implanted intraperitoneal sensors for telem etric monitoring of the animal's blood pressure. Other parameters meas ured at baseline included proteinuria and inulin clearance, After appr oximately 7 weeks all of the parameters were remeasured and animals ki lled for morphologic assessment of the kidney, Results The B +/- A rat s had lower levels of proteinuria than did the rats in group A (21 +/- 12 mg/day for B + A rats versus 59 +/- 24 mg/day for A rats, P< 0.05) . The degree of glomerulosclerosis in the B + A rats was also reduced markedly compared with that in A rats (12 +/- 4% for B + A rats versus 43 + 12% for A rats, P< 0.05), Moreover, the results on proteinuria a nd glomerulosclerosis of B + A rats were similar to those for B rats. These differences could not be explained totally in terms of differenc es in blood pressure control (144 +/- 12 mmHg in A rats versus 132 +/- 13 mmHg in B + A rats, NS). Conclusion The results were consistent wi th the observation that a combination of benzepril and amlodipine prov ides additional protection against renal injury compared with that pro vided by amlodipine alone, The mechanism for this benefit is not known .