Endothelium-dependent relaxation in the isolated rat kidney: impairment by cyclosporine A

Journal of Cardiovascular Pharmacology
D StephanM Barthelmebs

Abstract

The therapeutical use of cyclosporine A (CsA) is hampered by the development of nephrotoxicity characterized by a marked increase in renal vascular resistance (RVR). We investigated vascular functions in kidneys of rats treated with CsA. The ex vivo vascular reactivity of kidneys from control rats and animals treated subacutely with CsA [50 mg/kg/day subcutaneously (s.c.) for 16-21 days] or an olive oil vehicle (1 ml/kg) was analyzed in male Wistar rats. The right kidney was isolated and perfused with Tyrode's or Krebs solution in an open circuit. The effects of acetylcholine (Ach), fenoldopam (FEN), and sodium nitroprusside (SNP) on norepinephrine (NE) preconstricted kidneys were studied. In control kidneys (untreated or vehicle-treated), Ach induced a relaxation (EC50 = 0.56 +/- 0.05 x 10(-9)M; Emax = 88.2 +/- 2.1% decrease in the vascular tone restored by NE) which was endothelium-dependent [near-complete abolition after treatment with a detergent, 3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propane-sulfonate (CHAPS) treatment] but only partially inhibited by indomethacin (EC50 = 1.71 +/- 0.39 x 10(-9)M, p < 0.05; Emax = 87.1 +/- 4.9%, NS) or indomethacin with NG-nitro-L-arginine methyl ester (L-NAME: EC50 = 1.04 +/- 0.38 x 1...Continue Reading

Citations

Jul 8, 2000·European Journal of Pharmacology·G RomanoE Bartoli
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Mar 20, 2002·Pharmacology, Biochemistry, and Behavior·Houman HomayounAhmad Reza Dehpour
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Feb 8, 2003·Antioxidants & Redox Signaling·José M Valdivielso, Roland C Blantz
Jun 21, 2008·Clinical and Experimental Pharmacology & Physiology·Sahar M El-GowillyMahmoud M El-Mas
Apr 29, 1998·Kidney International·S E ThomasR J Johnson
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Oct 19, 2016·Acta Physiologica·M FählingC Rosenberger
Feb 14, 1998·Kidney International·R C Blantz

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