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).


CONCLUSIONS
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.
Bakris
G L
GL
Department of Preventive Medicine, Rush Hypertension Center, Rush-Presbyterian-St Luke's Medical Center, Chicago, Illinois 60612, USA.
Griffin
K A
KA
Picken
M M
MM
Bidani
A K
AK
D017311:Amlodipine / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000517:prevention & control* / Q000652:urine; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009392:Nephrectomy; D011507:Proteinuria / Q000378:metabolism / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D002121:Calcium Channel Blockers; D017311:Amlodipine; C044946:benazepril