[Changing of renal endothelium-dependent vascular reactivity by cyclosporin A].
Clinical use of the immunosuppressant cyclosporine A (CSA) is hampered by its nephrotoxicity. The renal vascular resistance is increased, may be as a consequence of a deleterious effect of the drug on the vascular endothelial cell function. The renal effects of a subchronic treatment with CSA (50 mg/kg/d, sc, 18 days), or olive oil vehicule (1 ml/kg), were studied in normotensive male Wistar rats. Creatinine clearance was measured on 24 h urine collection before the right kidney of the animals was isolated and perfused in an open circuit at 6 ml/min with Tyrode's solution. Renal vasodilator responses to acetylcholine (ACH, 10(-10) to 10(-7) M) and sodium nitroprusside (NP, 3 x 10(-9) to 3 x 10(-6) M) were studied after reestablishment of a renal vascular tone by a continuous perfusion of noradrenaline (NA, 10(-7) M). ACH was more potent than NP to induce renal vasodilation (EC50 = 0.57 +/- 0.05 x 10(-9) M, n = 8, vs 3.42 +/- 0.29 x 10(-8) M, n = 5), but both drugs reversed the NA-induced vasoconstriction by near 90%. L-NAME (3 x 10(-5) M) had no effect on NP-induced renal relaxation but suppressed responses to low concentrations of ACH and decreased by half its Emax (47 +/- 17%).(ABSTRACT TRUNCATED AT 250 WORDS)
Barthelmebs
M
M
Institut de pharmacologie (URA D0589 CNRS), université Louis-Pasteur, Strasbourg.
Billing
A
A
Stephan
D
D
Krieger
J P
JP
Grima
M
M
Imbs
J L
JL
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects
D009599:Nitroprusside; D009569:Nitric Oxide; D016572:Cyclosporine; D000109:Acetylcholine
Modification de la réactivité vasculaire rénale endothélium-dépendante par la ciclosporine A.