Endothelial dysfunction in renal transplant recipients maintained on cyclosporine

Background. Hypertension is almost universal following renal transplantatio n and may contribute to the already poor cardiovascular prognosis of this g roup. Cyclosporine-induced hypertension is a particular problem and has var iously been attributed to increased sympathetic nerve activity. salt and wa ter retention, and increased circulating endothelin levels. However. the ef fects of cyclosporine on the L-arginine/nitric oxide (NO) system in vivo in humans are unknown. In this present study, we examined basal and stimulate d NO production from the vascular endothelium in cyclosporine-treated renal transplant recipients using the technique of forearm venous plethysmograph y. Methods. In study 1, stimulated NO production was assessed in 9 cyclosporin e-treated renal transplant recipients (CsA). 7 azathioprine-treated renal t ransplant recipients (AZA). and 12 controls, using carbachol (an endotheliu m-dependent vasodilator) and sodium nitroprusside (an endothelium-independe nt vasodilator). In study 2, basal NO production was assessed in 9 cyclospo rine-treated patients and 11 controls using L-NMMA (inhibits NO synthase), with norepinephrine as a control vasoconstrictor. Drugs were infused into t he nondominant forearm through a sterile 27-gauge needle. and changes in fo rearm blood flow (FBF) were measured using venous occlusion plethysmography . Results. In study 1, sodium nitroprusside caused a similar dose-dependent i ncrease in FBF in all groups. However, the median (range) percentage increa se FBF to carbachol (3 mu g/min) was markedly reduced in the CsA patients ( 188.8. 72.5 to 385.1) compared with AZA patients (378.1. 124.0 to 548.9: P = 0.042) and to controls (303.8. 124.8 to 813.3, P = 0.028). In study 2, th e maximum percentage reduction in FBF to L-NMMA (4 mu mol/min) was less pro nounced in CsA patients (-19.5: -4.7 to -63.1) compared with controls (-39. 5: -15.7 to -52.8: P = 0.056), and while controls vasoconstricted to the ma ximum dose of norepinephrine (240 pmol/min) as expected (-26.9; -1.4 to -38 .6), CsA patients as a group tended to vasodilate (7.9. -36.8 to 92.6. P = 0.02). Conclusion. These data demonstrate impaired stimulated and basal NO product ion in CsA patients, indicating endothelial dysfunction. This may predispos e patients to atherosclerosis and may he involved in the etiology of post-t ransplant hypertension.