Endothelial dysfunction in renal transplant recipients maintained on cyclosporine

Morris, S. T.W., McMurray, J. J.V. , Rodger, R. S. C., Farmer, R. and Jardine, A. G. (2000) Endothelial dysfunction in renal transplant recipients maintained on cyclosporine. Kidney International, 57(3), pp. 1100-1106. (doi: 10.1046/j.1523-1755.2000.00937.x) (PMID:10720962)

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Abstract

Background: Hypertension is almost universal following renal transplantation and may contribute to the already poor cardiovascular prognosis of this group. Cyclosporine-induced hypertension is a particular problem and has variously been attributed to increased sympathetic nerve activity, salt and water retention, and increased circulating endothelin levels. However, the effects of cyclosporine on the l-arginine/nitric oxide (NO) system in vivo in humans are unknown. In this present study, we examined basal and stimulated NO production from the vascular endothelium in cyclosporine-treated renal transplant recipients using the technique of forearm venous plethysmography.<p></p> Methods: In study 1, stimulated NO production was assessed in 9 cyclosporine-treated renal transplant recipients (CsA), 7 azathioprine-treated renal transplant recipients (AZA), and 12 controls, using carbachol (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator). In study 2, basal NO production was assessed in 9 cyclosporine-treated patients and 11 controls using l-NMMA (inhibits NO synthase), with norepinephrine as a control vasoconstrictor. Drugs were infused into the nondominant forearm through a sterile 27-gauge needle, and changes in forearm blood flow (FBF) were measured using venous occlusion plethysmography.<p></p> Results: In study 1, sodium nitroprusside caused a similar dose-dependent increase in FBF in all groups. However, the median (range) percentage increase FBF to carbachol (3 μg/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, the maximum percentage reduction in FBF to l-NMMA (4 μmol/min) was less pronounced 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 maximum 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).<p></p> Conclusion: These data demonstrate impaired stimulated and basal NO production in CsA patients, indicating endothelial dysfunction. This may predispose patients to atherosclerosis and may be involved in the etiology of post-transplant hypertension.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McMurray, Professor John and Jardine, Professor Alan
Authors: Morris, S. T.W., McMurray, J. J.V., Rodger, R. S. C., Farmer, R., and Jardine, A. G.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Kidney International
Publisher:Nature Publishing Group
ISSN:0085-2538
ISSN (Online):1523-1755

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