Endothelial dysfunction in renal transplant recipients maintained on cyclosporine

• Published in: Kidney international Vol. 57; no. 3; pp. 1100 - 1106
• Main Authors: Morris, Scott T.W., Mcmurray, John J.V., Rodger, R. Stuart C., Farmer, Rosemary, Jardine, Alan G.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01-03-2000; Nature Publishing; Elsevier Limited
• Subjects: Adult; Azathioprine - therapeutic use; Biological and medical sciences; Carbachol - therapeutic use; cardiovascular disease; Cyclosporine - therapeutic use; Drug toxicity and drugs side effects treatment; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Enzyme Inhibitors - pharmacology; Female; Forearm - blood supply; forearm plethysmography; Humans; hypertension; Immunosuppressive Agents - therapeutic use; Kidney Transplantation; Male; Medical sciences; Middle Aged; Nitric Oxide - biosynthesis; Nitroprusside - pharmacology; omega-N-Methylarginine - pharmacology; Pharmacology. Drug treatments; Postoperative Period; Regional Blood Flow - drug effects; renal transplantation; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; Toxicity: urogenital system; vascular endothelium; Vasodilator Agents - pharmacology; cardiovascular disease; vascular endothelium; hypertension; renal transplantation; forearm plethysmography; Kidney disease; Human; Hypertension; Postoperative; Urinary system disease; Toxicity; Homograft; Cardiovascular disease; Transplantation; Kidney; Surgery; Nitric oxide; Atherosclerosis; Complication; Ciclosporin
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1046/j.1523-1755.2000.00937.x

Endothelial dysfunction in renal transplant recipients maintained on cyclosporine.
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.
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.
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).
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.