Oxidative stress and TGFbeta in kidney-transplanted patients with cyclosporin-induced hypertension. Effect of carvedilol and nifedipine.
Clin Nephrol
; 58(2): 103-10, 2002 Aug.
Article
en En
| MEDLINE
| ID: mdl-12227681
ABSTRACT
Cyclosporin is a powerful stimulator of oxidative stress signaling, leading to TGFbeta production, NO degradation, endothelial dysfunction, hypertension and post-transplant nephropathy. Carvedilol, alpha1-beta-blocker with strong antioxidant activity, may interfere with this chain of events. Therefore, we measured monocyte ecNOS, TGFbeta 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 TGFbeta 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 TGFbeta, a key fibrogenic cytokine, and by activating HO-1 production.
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Bases de datos:
MEDLINE
Asunto principal:
Propanolaminas
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Tirosina
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Carbazoles
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Bloqueadores de los Canales de Calcio
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Nifedipino
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Factor de Crecimiento Transformador beta
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Trasplante de Riñón
/
Ciclosporina
/
Estrés Oxidativo
/
Antagonistas Adrenérgicos beta
Tipo de estudio:
Clinical_trials
/
Etiology_studies
Límite:
Adult
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Clin Nephrol
Año:
2002
Tipo del documento:
Article