Oxidative stress and nitric oxide system in post-transplant hypertension

Background: CsA-induced endothelial dysfunction and CsA-induced hypertensio n have been attributed to CsA effects on the endothelial-derived factors co ntrolling vasomotor tone, but the mechanisms responsible are unclear. Endot helial nitric oxide (NO) is known to maintain a state of basal vasodilation and recently a NO mediated counterregulatory mechanism protective from CsA -induced vasoconstriction has been suggested. Patients and methods: Our stu dy evaluates ecNOS gene status and NO metabolites in kidney transplanted pa tients under chronic CsA treatment with CsA-induced hypertension, Since CsA increases superoxide production, which metabolizes NO, plasma hydroperoxid es and peroxynitrite were also evaluated as index of the presence of "oxida tive stress". Results: Quantification of monocyte ecNOS mRNA and NO metabol ites plasma level from patients and control subjects (C) demonstrated NO sy stem up regulation in patients notwithstanding hypertension. The mean ecNOS to beta-actin ratio was 2.00 +/- 0.87 vs 0.29 +/- 0.08 in C, p < 0.04. NO metabolite plasma level was 30.03 +/- 9.62 mM vs 9.37 +/- 3.86. p < 0.001. Hydroperoxides were also increased in patients: 3.6 +/- 1.6 i.a.u. vs 1.4 /- 0.. p < 0.007 (from cholesterol esters) and 10.8 +/- 6.6 vs 1.5 +/- 0.9, p < 0.008 (from triglycerides) as well as peroxynitrite plasma level: 0.36 +/- 0.14 mM/L vs undetectable in C. Conclusions: This study confirms a NO system up-regulation in transplanted patients. However. the counterregolato ry system to CsA-induced vasoconstriction. could be cancelled by CsA induce d superoxide and free radicals production which, increasing NO metabolism c ould contribute to CsA induced vasoconstriction and hypertension.