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

Abstract

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.

• Authors: G L Bakris, K A Griffin, M M Picken, A K Bidani
• Journal: Journal of hypertension (J Hypertens) Vol. 15 Issue 10 Pg. 1181-5 (Oct 1997) ISSN: 0263-6352 [Print] England
• PMID: 9350593 (Publication Type: Journal Article)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Benzazepines
• Calcium Channel Blockers
• Amlodipine
• benazepril

Topics

• Amlodipine (pharmacology)
• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Benzazepines (pharmacology)
• Blood Pressure (drug effects)
• Calcium Channel Blockers (pharmacology)
• Disease Models, Animal
• Drug Therapy, Combination
• Glomerulosclerosis, Focal Segmental (etiology, prevention & control, urine)
• Kidney (drug effects)
• Male
• Nephrectomy
• Proteinuria (metabolism, prevention & control)
• Random Allocation
• Rats
• Rats, Sprague-Dawley