Combined effects of an angiotensin converting enzyme inhibitor and a calcium antagonist on renal injury

Background Angiotensin converting enzyme inhibitors have uniformly been shown to prevent the development both of proteinuria and of glomerulosclerosis 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 angiotensin converting enzyme inhibitor and a DCA would lead to a smaller increase both in proteinuria and in glomerulosclerosis relative to that caused by administration of a DCA alone at similar levels of blood pressure. Methods Experiments were carried out using Sprague-Dawley rats that had been subjected to five-sixths renal ablation. Animals were allocated randomly to one of four groups: control (no treatment), amlodipine (A rats), benazepril (B rats), or a combination of benazepril and amlodipine (B + A rats). We implanted intraperitoneal sensors for telemetric monitoring of the animal's blood pressure. Other parameters measured at baseline included proteinuria and inulin clearance, After approximately 7 weeks all of the parameters were remeasured and animals killed for morphologic assessment of the kidney, Results The B +/- A rats 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 and glomerulosclerosis of B + A rats were similar to those for B rats. These differences could not be explained totally in terms of differences in blood pressure control (144 +/- 12 mmHg in A rats versus 132 +/- 13 mmHg in B + A rats, NS). Conclusion The results were consistent with the observation that a combination of benzepril and amlodipine provides additional protection against renal injury compared with that provided by amlodipine alone, The mechanism for this benefit is not known.