Abstract

Cyclosporin is a powerful stimulator of oxidative stress signaling, leading to TGFb production, NO degradation, endothelial dysfunction, hypertension and post-transplant nephropathy. Carvedilol, a1-b-blocker with strong antioxidant activity, may interfere with this chain of events. Therefore, we measured monocyte ecNOS, TGFb and heme oxygenase-1 (HO-1) mRNA level and plasma nitrite/nitrate, 3-nitrotyrosine, an estimate of peroxynitrite, and total plasma antioxidant power in kidney-transplanted patients with post-transplant hypertension, before and after treatment with carvedilol, 25 – 50 mg o.d. orally for 4 months (n = 15). The dihydropyridine calcium channel blocker nifedipine (n = 10) was used as comparator antihypertensive drug. Blood pressure fell to a similar extent with both drugs. Carvedilol increased plasma antioxidant power and HO-1 mRNA and reduced 3-nitrotyrosine and TGFb mRNA levels, while the same was not observed with nifedipine. Monocyte ec NOS mRNA levels and plasma nitrite/nitrate were higher in the patients than in a normotensive healthy control group and were unaffected by either treatment. In conclusion, carvedilol reduces the oxidative stress and corrects the altered cellular signaling mediated by oxidative stress in CsA-induced post-transplant hypertension. Therefore, it may prevent long-term complications, such as endothelial dysfunction, fibrogenesis and post-transplant nephropathy by decreasing NO degradation and production of TGFb, a key fibrogenic cytokine, and by activating HO-1 production.

Author Details

Authors

• L. Calò¹
• B. Giacon²
• P.A. Davis³
• E. Pagnin¹
• A. Piccin¹
• P. Riegler²
• W. Huber²
• A. Antonello⁴
• A. Semplicini¹

Departments

• ¹ Department of Clinical and Experimental Medicine, Clinica Medica
• ⁴  and
• ² Nephrology, University of Padua,
• ³ Department of Internal Medicine, University of California, Davis, USA, and
• ⁴ Division of Nephrology Bolzano Hospital, Italy

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Citation