Forearm vasorelaxation in hypertensive renal transplant patients: The impact of withdrawal of cyclosporine

Objective. To determine whether cyclosporine A-induced hypertension in renal transplant recipients is accompanied by impairment of endothelium-dependent vasodilatation, which has been suggested by in-vitro and in-vivo animal experiments. Design and methods. In-vivo endothelium-dependent and endothelium-independent vasodilatation, and plasma concentrations of vasoactive hormones in 16 renal transplant patients were determined while they were being treated with cyclosporine A, and 16 weeks later, after their treatment had been changed to azathioprine therapy. The vasodilator response of the forearm vascular bed was measured by strain gauge venous occlusion plethysmography during intra-arterial infusion of acetylcholine (endothelium-dependent vasodilatation) and nitroprusside (endothelium-independent vasodilatation). Postischemic reactive flow was measured after 10 min of arterial occlusion. In addition, plasma concentrations of norepinephrine, and the prostanoids prostaglandin E2 and thromboxane B2, and also concentration of cyclosporine A in blood, were measured. Glomerular filtration rate and renal blood flow were estimated 1 day before the plethysmography study during each treatment period. Results. Upon changing from cyclosporine A to azathioprine treatment, mean arterial pressure fell significantly by 12 ± 3% (P < 0.05). Glomerular filtration rate and renal blood flow increased by 13 ± 5 and 19 ± 8%, respectively (both P < 0.05), while renal vascular resistance fell by 48 ± 11% (P < 0.01). Both baseline forearm blood flow and baseline forearm resistance did not change after conversion (5.7 ± 0.7 versus 4.9 ± 0.6 ml/100 ml/min, and 27.3 ± 4.2 versus 26.2 ± 3.2 arbitrary units). The absolute and relative forearm blood flow responses, and forearm vascular resistance responses to infusions of acetylcholine and nitroprusside were similar during treatments with cyclosporine A and azathioprine. Peak postischaemic forearm blood flow was 42 ± 12% higher during cyclosporine A treatment than it was during azathioprine treatment (P < 0.05), but the minimal postischaemic forearm vascular resistance did not differ for these treatments. Plasma prostaglandin E2 and thromboxane B2 levels decreased by 34 ± 7 and 45 ± 8%, respectively, after changing treatment, but norepinephrine levels did not change. Conclusions. Our data indicate that cyclosporine A-induced hypertension in renal transplant recipients is not accompanied by an increase in forearm vascular resistance. In addition, changing from cyclosporine A to azathioprine treatment did not cause changes in endothelial vasodilator functioning, although mean arterial pressure decreased significantly. Our results do not support the hypothesis that attenuation of endothelial vasodilator functioning contributes to the development of cyclosporine A-induced hypertension.

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