Endothelial dysfunction in renal transplant recipients maintained on cyclosporine

被引:123
作者
Morris, STW
McMurray, JJV
Rodger, RSC
Farmer, R
Jardine, AG
机构
[1] Western Infirm & Associated Hosp, Renal Unit, Dept Med & Therapeut, Glasgow G11 6NT, Lanark, Scotland
[2] Western Infirm & Associated Hosp, Dept Cardiol, Glasgow G11 6NT, Lanark, Scotland
关键词
renal transplantation; hypertension; cardiovascular disease; forearm plethysmography; vascular endothelium;
D O I
10.1046/j.1523-1755.2000.00937.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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. 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. 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 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, the maximum percentage reduction in FBF to L-NMMA (4 mu mol/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). Conclusion. These data demonstrate impaired stimulated and basal NO production in CsA patients, indicating endothelial dysfunction. This may predispose patients to atherosclerosis and may he involved in the etiology of post-transplant hypertension.
引用
收藏
页码:1100 / 1106
页数:7
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