Oxidative stress and nitric oxide system in post-transplant hypertension.
BACKGROUND
CsA-induced endothelial dysfunction and CsA-induced hypertension have been attributed to CsA effects on the endothelial-derived factors controlling vasomotor tone, but the mechanisms responsible are unclear. Endothelial 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.


METHODS
Our study evaluates ecNOS gene status and NO metabolites in kidney transplanted patients under chronic CsA treatment with CsA-induced hypertension. Since CsA increases superoxide production, which metabolizes NO, plasma hydroperoxides and peroxynitrite were also evaluated as index of the presence of "oxidative stress".


RESULTS
Quantification of monocyte ecNOS mRNA and NO metabolites plasma level from patients and control subjects (C) demonstrated NO system 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 +/- 0.8, 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 counterregolatory system to CsA-induced vasoconstriction, could be cancelled by CsA induced superoxide and free radicals production which, increasing NO metabolism could contribute to CsA induced vasoconstriction and hypertension.
Calò
L
L
Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova, Italy.
Marcon
R
R
Rigotti
P
P
Pagnin
E
E
Mennella
G
G
Spinello
M
M
Bonfante
L
L
Cantaro
S
S
D'Angelo
A
A
Semplicini
A
A
Antonello
A
A
D006801:Humans; D006977:Hypertension, Renal / Q000209:etiology / Q000378:metabolism*; D016030:Kidney Transplantation / Q000009:adverse effects; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D019459:Urothelium / Q000378:metabolism
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase