Egyptian Journal of Basic and Clinical Pharmacology

Egyptian Journal of Basic and Clinical Pharmacology
Vol. 3 (2013), Issue 2, pp. 31-41
doi:10.11131/2013/101346

Alfacalcidol Enhances the Protective Effects of Lisinopril against Nephrosclerosis in a Rat Model of Hypertensive Nephropathy

Background and aim: The efficiency of renin-angiotensin system (RAS) blockade against the progression of end stage renal disease is limited because of the compensatory renin rise, the other way round vitamin D suppresses renin biosynthesis. In the present study the effect of low dose alfacalcidol on the progression of renal injury and the impact of its combination with lisinopril in a model of hypertensive nephropathy induced by NG-nitro-L-arginine methyl ester (L-NAME) in rats was investigated. Methods: Five groups of rats were used: Vehicle control group; L-NAME group (50 mg/kg); L-NAME and lisinopril (10 mg/kg) group; L-NAME and low dose alfacalcidol (0.1ug/kg) group, alfacalcidol and lisinopril group. All substances were given daily for 8 weeks by gavage. Systolic blood pressure (SBP) was monitored at base line and by the end of the 8th week. Thereafter urine and blood samples were collected for renal function, plasma calcium, phosphorus fibroblast growth factor 23 (FGF23) and 1, 25-(OH)2 vitamin D measurements. Kidneys were isolated for histopathological examinations. Results: Lisinopril significantly reduced elevated SBP, improved renal dysfunction induced by L-NAME compared to alfacalcidol. Alfacalcidol , significantly limited the interstitial fibrosis (15%) as well as glomerulosclerosis (33%) compared with L-NAME and lisinopril treated group despite having lower effect than lisinopril on the elevated SBP induced by L-NAME. Alfacalcidol reduced plasma renin activity (PRA) increased by both L-NAME and lisinopril. Alfacalcidol had no significant effect on plasma FGF23 but lisinopril reduced it. A significant increase in 1,25 -(OH)2 vitamin D level was evident with lisinopril and alfacalcidol (12.6% and 22.43%) compared to L-NAME group. Conclusion: Alfacalcidol exhibited renoprotective effects by correction of vitamin D deficiency induced by L-NAME and reduction in PRA induced by lisinopril . Combined lisinopril and alfacalcidol treatment had a more protective effect than either agent alone.