Renal functional and histomorphological evaluation of cyclosporin A-verapamil interaction in male rats

ABSTRACT

Cyclosporin A [CyA] therapy is often associated with nephrotoxicity partly due to abnormalities in intracellular calcium signaling. Pharmacological, biochemical, and histopathological studies were undertaken in the present study to investigate the potential protective effect of the L-type calcium channel blocker, verapamil [VER], against CyA -induced renal damage. Rats were treated for 10 days with olive oil [control], CyA [20 mg/kg, orally], VER [10 mg/kg, intraperitoneally], or CyA plus VER. The vascular reactivity of the isolated perfused kidney to endothelium-dependent and independent relaxation induced by acetylcholine [ACh] and sodium nitroprusside [SNP], respectively; was evaluated ACh [100 nmol] caused 77.23 +/- 8.11% reduction in the renal perfusion pressure and this effect was significantly reduced by CyA treatment [51.99 +/- 5.13%]. In contrast, vasodilatory responses to SNP [100 micro M] were significantly potentiated in CyA-treated compared to control rats [95.28 +/- 5.38% vs. 43.79 +/- 2.69%]. CyA increased plasma urea and creatinine, indices of renal function, and caused moderate renal tubular vacuolization. Unlike CyA. treatment with VER produced no change in the studied parameters. In rats co-treated with CyA and VER, the attenuation in ACh relaxation was maintained [54.01 +/- 7.31%] whereas the potentiation of SNP relaxation was exaggerated [13 7.31 +/- 17.68%], and microscopical abnormalities were aggravated compared with CyA -treated rats. The present results indicate that, contrary to our expectations, VER exacerbates rather than ameliorates functional and structural features of CyA nephrotoxicity in rats