Journal of the American Society of Nephrology, Vol 2, 1291-1297, Copyright © 1992 by American Society of Nephrology

REGULAR ARTICLES

Chronic cyclosporine therapy impairs endothelium-dependent relaxation in the renal artery of the rat

D Diederich, Z Yang and TF Luscher
Department of Research, University Hospital, Basel, Switzerland.

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.

This article has been cited by other articles:

				D. Ramzy, L. C. Tumiati, E. Tepperman, R. Sheshgiri, J. Jackman, M. Badiwala, and V. Rao Dual immunosuppression enhances vasomotor injury: Interactive effect between endothelin-1 and nitric oxide bioavailability. J. Thorac. Cardiovasc. Surg., April 1, 2008; 135(4): 938 - 944. [Abstract] [Full Text] [PDF]

				N. A. Bobadilla and G. Gamba New insights into the pathophysiology of cyclosporine nephrotoxicity: a role of aldosterone Am J Physiol Renal Physiol, July 1, 2007; 293(1): F2 - F9. [Abstract] [Full Text] [PDF]

				D. Ramzy, V. Rao, L. C. Tumiati, N. Xu, S. Miriuka, D. Delgado, and H. J. Ross Role Of Endothelin-1 and Nitric Oxide Bioavailability in Transplant-Related Vascular Injury: Comparative Effects of Rapamycin and Cyclosporine Circulation, July 4, 2006; 114(1_suppl): I-214 - I-219. [Abstract] [Full Text] [PDF]

				N. A. Bobadilla, E. Tapia, F. Jimenez, L. G. Sanchez-Lozada, J. Santamaria, A. Monjardin, A. Bolio, G. Gamba, and J. Herrera-Acosta Dexamethasone increases eNOS gene expression and prevents renal vasoconstriction induced by cyclosporin Am J Physiol Renal Physiol, September 1, 1999; 277(3): F464 - F471. [Abstract] [Full Text] [PDF]

				N. A. Bobadilla, G. Gamba, E. Tapia, R. Garcia-Torres, A. Bolio, P. Lopez-Zetina, and J. Herrera-Acosta Role of NO in cyclosporin nephrotoxicity: effects of chronic NO inhibition and NO synthases gene expression Am J Physiol Renal Physiol, April 1, 1998; 274(4): F791 - F798. [Abstract] [Full Text] [PDF]

				L.-T. Dijkhorst-Oei, T. J. Rabelink, P. Boer, and H. A. Koomans Nifedipine Attenuates Systemic and Renal Vasoconstriction During Nitric Oxide Inhibition in Humans Hypertension, May 1, 1997; 29(5): 1192 - 1198. [Abstract] [Full Text]

				E. S.G. Stroes, T. F. Luscher, F. G. de Groot, H. A. Koomans, and T. J. Rabelink Cyclosporin A Increases Nitric Oxide Activity In Vivo Hypertension, February 1, 1997; 29(2): 570 - 575. [Abstract] [Full Text]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673