Nifedipine prevents changes in nitric oxide synthase mRNA levels induced by cyclosporine

Cyclosporine toxicity mainly affects kidney and liver function. We have pre viously shown that cyclosporine nephrotoxicity alters kidney nitric oxide s ynthase mRNA pattern of expression. To determine if nitric oxide synthase e xpression changes are mediated directly by cyclosporine or by secondary hem odynamic alterations induced by cyclosporine, we evaluated if these effects are tissue specific and if nifedipine-induced vasodilation prevents these alterations. Uninephrectomized Wistar rats treated for 7 days with olive oi l, cyclosporine (30 mg/kg), nifedipine (3 mg/kg), and nifedipine+cyclospori ne were studied. In vehicle and cyclosporine groups, the gene expression of the neuronal, inducible, and endothelial nitric oxide synthases in cerebel lum, heart, intestine, liver, renal cortex, and medulla was evaluated. The administration of cyclosporine was associated with nephrotoxicity and hepat otoxicity, increased endothelial nitric oxide synthase mRNA levels in renal cortex and liver, and a decrease in inducible nitric oxide synthase and ne uronal nitric oxide synthase in renal medulla. The mRNA levels of the 3 nit ric oxide synthase isoforms were not affected in any other tissue. Nifedipi ne did not alter nitric oxide synthase expression in the control group but prevented changes associated with cyclosporine. These results suggest that cyclosporine-induced changes in the pattern of expression of the nitric oxi de syntheses may be secondary to its hemodynamic effects.