ISSN:
1432-2277
Schlagwort(e):
Key words ecNOS
;
Nitric oxide
;
Cyclosporine
;
Hypertension
;
Superoxide anions
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Abstract Hypertension is a major side effect of cyclosporin (CsA). While the mechanism(s) responsible are unclear, CsA-induced endothelial dysfunction and CsA-induced hypertension have been attributed to the CsA effect on the endothelial-derived factors controlling vasomotor tone. Endothelial nitric oxide (NO) is crucial in the maintenance of a state of basal vasodilation, and recent studies have suggested an NO-mediated counterregulatory mechanism protective from CsA-induced vasoconstriction. Our study evaluates endothelial nitric oxide synthase (ecNOS) gene status (PCR analysis) and plasma levels of NO metabolites (ELISA) in kidney and heart transplant patients under chronic CsA treatment with CsA-induced hypertension. Since CsA increases superoxide production, which metabolises NO, plasma hydroperoxides from cholesterol esters and from triglycerides and peroxynitrite were also evaluated (HPLC) as an index of the presence of superoxides and of “oxidative stress”. Quantification of monocyte ecNOS mRNA and NO metabolites plasma levels from patients and controls (C) demonstrated NO system upregulation in patients notwithstanding the hypertension. The mean ecNOS to β-actin ratio was 1.80 ± 0.85 in patients vs 0.40 ± 0.09 in C (P 〈 0.04). NO metabolites were 34.03 ± 14.32 μM in patients vs 11.53 ± 5.64 μM in C (P 〈 0.001). Hydroperoxides from cholesterol esters and from triglycerides were also increased in patients, 3.4 ± 1.4 vs 1.3 ± 0.6 integrated area units (i. a. u.), P 〈 0.007 and 10.6 ± 6.4 vs 1.3 ± 0.8 i. a. u., P 〈 0.008, respectively, as well as the peroxynitrite plasma level, 0.32 ± 0.11 μM/l vs undetectable in C. This study confirms a CsA-induced NO system upregulation in transplanted patients. However, the NO-mediated counterregulatory system to CsA-induced vasoconstriction, present in normals, could be canceled in patients by CsA-induced superoxide (O2 –) and free radical production which, by increasing NO metabolism, could contribute to CsA-induced vasoconstriction and hypertension and predispose to atherosclerosis.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/s001470050374
Permalink
