Better microvascular function on long-term treatment with lisinopril than with nifedipine in renal transplant recipients

Background, The prevalence of hypertension in renal transplant recipients i s high but the pathophysiology is poorly defined. Impaired endothelial func tion map be a factor of major importance. The present study addresses the e ffects of long-term treatment with either lisinopril or slow-release nifedi pine on microvascular function and plasma endothelin in renal transplant re cipients on cyclosporin A (CsA). Methods, Seventy-five hypertensive renal transplant recipients were double- blind randomized to receive slow-release nifedipine (NIF, n = 40) or lisino pril (LIS, n=35). Ten normotensive, age-matched recipients served as contro ls. All patients received CsA-based immunosuppressive therapy including pre dnisolone and azathioprine. Microvascular function was assessed in the fore arm skin vasculature, using laser Doppler flowmetry in combination with pos t-occlusive reactive hyperaemia and endothelial-dependent function during l ocal acetylcholine (ACh) stimulation. Results, The analysis of microvascular function (AUC(rh)) showed that nifed ipine-treated patients had significantly lower responses compared with lisi nopril-treated patients (20 +/- 17 and 43 +/- 20 AU x min respectively, P=0 .0016). Endothelial function was borderline significantly lower in the NIF group compared with the LIS group (640 +/- 345 and 817 +/- 404 AU x min res pectively, P=0.056). The responses in the LIS group were comparable with th ose in non-hypertensive controls (AUC(rh) was 37 +/- 16 and AUC(ACh) was 99 4 +/- 566 AU x min). Plasma endothelin-1 concentrations were significantly higher in the NIF group compared with the LIS group (0.44 +/-0.19 vs 0.34 /-0.10 fmol/ml respectively, P=0.048), and were 0.29 +/-0.09 fmol/ml in the control patients. AUC(ACh) was associated with plasma endothelin-1 (P=0.00 53), while AUC(rh) was not (P=0.080). Conclusions. The study indicates that long-term treatment with lisinopril, when compared with nifedipine, yields a more beneficial effect on microvasc ular function in hypertensive renal transplant recipients on CsA. The benef icial microvascular effect may be mediated in part by an endothelin-1-assoc iated effect on the endothelium.