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      Beneficial Effect of the Long-Term Treatment with the Combination of an ACE Inhibitor and a Calcium Channel Blocker on Renal Injury in Rats with 5/6 Nephrectomy

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          The effects of the addition of a calcium channel blocker, verapamil (20 mg/kg/day) to an ACE inhibitor, trandolapril (0.7 mg/kg/day) in a 6-month treatment on renal insufficiency development in rats with 5/6th nephrectomy, were studied. Every month we measured heart rate and arterial pressure by the tail-cuff method. Renal function studies were performed in metabolic cages. At the end of the study, renal tissue was prepared for light microscope analysis. Renal lesions were assessed by semiquantitative scores in a blind fashion. Corpuscular section area, intraglomerular and tubulointerstitial fibrosis were determined by digital image analysis with a specific software (Fibrosis HR<sup>®</sup>) on syrium red-stained renal sections. Trandolapril markedly increased the survival ratio that after 6 months reached 87% in comparison with 61% in untreated rats. No mortality was observed in rats treated with the combination of verapamil and trandolapril. Trandolapril treatment prevented the development of hypertension. The combination verapamil-trandolapril did not induce further reduction on blood pressure. The untreated group showed a marked proteinuria, that in the trandolapril group showed an important reduction. The verapamil + trandolapril group showed a proteinuria significantly smaller than that of all the other groups. Light microscopy semiquantitative studies of the renal injury showed that the trandolapril and verapamil + trandolapril groups had a marked reduction in glomerular and tubulointerstitial alterations, compared with untreated animals. Quantitative determinations of glomerular and interstitial fibrosis performed on syrium red-stained renal sections demonstrated that fibrosis was reduced when rats when treated with trandolapril and even more with verapamil + trandolapril when they were compared to untreated animals’ values. In conclusion, long-term treatment with verapamil given in addition to trandolapril produces additional protection against progressive renal injury associated to subtotal nephrectomy.

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          Calcium antagonists and renal protection. Current status and future perspectives.

          During the past decade, considerable attention has been focused on the effects of calcium antagonists on renal function. Direct in vivo and in vitro observations in diverse experimental models indicate that calcium antagonists antagonize preglomerular vasoconstriction. Furthermore, calcium antagonists are postulated to have additional properties that contribute to their ability to afford renal protection. These putative mechanisms include the ability to retard renal growth, and possibly to attenuate mesangial entrapment of macromolecules, and to attenuate the mitogenic effects of diverse growth factors. Although the clinical implications of the above-mentioned findings have not been fully delineated, the results of recent clinical trials indicate that calcium antagonists exert salutary effects on renal function in clinical settings characterized by impaired renal hemodynamics, including transplant-associated acute renal insufficiency and, possibly, cyclosporine nephrotoxicity. Evidence has accrued suggesting that calcium antagonists may also be protective against acute radiocontrast-induced nephrotoxicity. Finally, the renal hemodynamic and natriuretic effects of calcium antagonists commend their use as antihypertensive agents in the management of essential hypertension, renovascular hypertension, and transplant-associated hypertension.

            Author and article information

            Nephron Exp Nephrol
            Cardiorenal Medicine
            S. Karger AG
            February 1998
            04 February 1998
            : 6
            : 1
            : 39-49
            Instituto Reina Sofía de Investigación Nefrológica, Departments of a Physiology and Pharmacology, and b Histology, Faculty of Medicine, University of Salamanca, Spain
            20503 Exp Nephrol 1998;6:39–49
            © 1998 S. Karger AG, Basel

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            Figures: 7, Tables: 3, References: 44, Pages: 11
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