Document Detail

Oxidative stress in kidney transplant patients with calcineurin inhibitor-induced hypertension: effect of ramipril.
MedLine Citation:
PMID:  12352326     Owner:  NLM     Status:  MEDLINE    
In patients with cyclosporine-induced hypertension, upregulation of the nitric oxide system and oxidative stress were shown, which could induce hypertension, remodeling, and chronic rejection by increasing nitric oxide catabolism. However, it is still debated whether cyclosporine and tacrolimus exert a different action. The aim of the current study was to compare the effects of cyclosporine and tacrolimus on markers of oxidative stress and endothelial dysfunction in kidney transplant patients with posttransplant hypertension. Monocyte p22, a NADH/NADPH system subunit, transforming growth factor-beta (TGF-beta), heme oxygenase-1 (HO-1), and endothelial NOS gene expression were measured in 16 patients. Angiotensin II is a potent stimulator of oxidative stress and angiotensin-converting enzyme inhibition may blunt this effect. Therefore, the same parameters were measured before and after 2 months of treatment with ramipril (5 mg/d). At baseline, in cyclosporine-and tacrolimus-treated patients, p22 and TGF-beta mRNA were similarly increased in comparison with normotensive healthy controls (0.90 +/- 0.05 d.u. and 0.83 +/- 0.05 in cyclosporine, 0.89 +/- 0.07 and 0.84 +/- 0.05 in tacrolimus; 0.53 +/- 0.07 and 0.75 +/- 0.03 in controls, respectively; p < 0.001). Endothelial NOS mRNA was increased in cyclosporine-and tacrolimus-treated patients in comparison with controls (0.92 +/- 0.09, 0.96 +/- 0.04, and 0.37 +/- 0.05 respectively; p < 0.001), whereas no difference was found between patients and controls in HO-1 mRNA. Ramipril reduced blood pressure (from 140 +/- 11/91 +/- 7 mm Hg to 129 +/- 6/85 +/- 5 mm Hg in cyclosporine and from 138 +/- 7/92 +/- 7 mm Hg to 127 +/- 10/82 +/- 6 mm Hg in tacrolimus group; p < 0.02 with no difference between groups). Ramipril also reduced p22 (to 0.83 +/- 0.05 in cyclosporine, p < 0.03 and to 0.81 +/- 0.08 in tacrolimus; p < 0.01) and TGF-beta mRNA (to 0.72 +/- 01 in cyclosporine, p < 0.02, and to 0.73 +/- 0.05 in tacrolimus; p < 0.01) with no difference between groups, but it did not change HO-1 and ecNOS mRNA. Cyclosporine and tacrolimus induce a comparable oxidative stress in kidney transplant patients with posttransplant hypertension. The association of ramipril normalizes blood pressure and reduces the oxidative stress induced by both drugs.
Lorenzo A Calò; Paul A Davis; Bruno Giacon; Elisa Pagnin; Michelangelo Sartori; Peter Riegler; Augusto Antonello; Walter Huber; Andrea Semplicini
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  40     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-09-27     Completed Date:  2003-03-05     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  625-31     Citation Subset:  IM    
Department of Clinical and Exprimental Medicine, Clinica Medica 4, University of Padova, Padova, Italy.
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MeSH Terms
Analysis of Variance
Angiotensin-Converting Enzyme Inhibitors / therapeutic use
Calcineurin / antagonists & inhibitors*,  metabolism
Gene Expression Regulation / drug effects,  physiology
Hypertension / chemically induced,  drug therapy*,  metabolism
Immunosuppressive Agents / adverse effects,  pharmacology
Kidney Transplantation*
Middle Aged
Monocytes / drug effects,  metabolism
Oxidative Stress / drug effects*,  physiology
Ramipril / therapeutic use*
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Immunosuppressive Agents; 87333-19-5/Ramipril; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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