Chronic cyclosporine therapy impairs endothelium-dependent relaxation in the renal artery of the rat.
Cyclosporine is an immunosuppressive substance that causes structural and functional alterations in endothelial cells. To examine the effects of chronic cyclosporine therapy on endothelial function, Wistar Kyoto rats received daily s.c. injections of saline, cyclosporine solvent, or cyclosporine (15, 30, or 50 mg/kg) for up to 2 wk. Blood pressure remained unchanged in all groups. Segments of the renal artery were suspended in organ chambers filled with physiological salt solution, and isometric tension was recorded. In rats treated with 30 or 50 mg/kg/day of cyclosporine, endothelium-dependent relaxations to acetylcholine of the renal artery were significantly impaired when compared with vessels obtained from rats injected with saline or solvent. The reduced acetylcholine-induced relaxation of cyclosporine-treated vessels was improved by preincubation of the preparations with the cyclooxygenase inhibitor indomethacin. Endothelium-independent relaxations in response to sodium nitroprusside were unimpaired in renal artery rings after 1 wk of cyclosporine but were reduced after 2 wk of treatment with 30 mg/kg/day. Contractions of the renal artery in response to norepinephrine and serotonin were not altered by cyclosporine. Thus, (1) high-dose cyclosporine therapy impairs endothelium-dependent relaxations in the renal artery of the rat; (2) an endothelium-derived cyclooxygenase product reduces the effects of endothelium-derived relaxing factor in cyclosporine-treated rats; and (3) chronic cyclosporine treatment slightly impairs vascular smooth muscle relaxation, whereas vascular contractility remains unaltered.
Diederich
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D
Department of Research, University Hospital, Basel, Switzerland.
Yang
Z
Z
Lüscher
T F
TF
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology
D009599:Nitroprusside; D012701:Serotonin; D016572:Cyclosporine; D000109:Acetylcholine; D009638:Norepinephrine