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6792423 
Journal Article 
Differential effects of selective cyclooxygenase-2 inhibitors on endothelial function in salt-induced hypertension 
Hermann, M; Gay, RE; Gay, S; Luscher, TF; Ruschitzka, F; Camici, G; Fratton, A; Hurlimann, D; Tanner, FC; Hellermann, JP; Fiedler, M; Thiery, J; Neidhart, M; , 
2003 
Yes 
Circulation
ISSN: 0009-7322
EISSN: 1524-4539 
LIPPINCOTT WILLIAMS & WILKINS 
PHILADELPHIA 
2308-2311 
14597594 
WOS:000186475200004 
Background-In view of the ongoing controversy about potential differences in cardiovascular safety of selective cyclooxygenase (COX)-2 inhibitors (coxibs), we compared the effects of 2 different coxibs and a traditional NSAID on endothelial dysfunction, a well-established surrogate of cardiovascular disease, in salt-induced hypertension.Methods and Results-Salt-sensitive (DS) and salt-resistant (DR) Dahl rats were fed a high-sodium diet (4% NaCl) for 56 days. From days 35 to 56, diclofenac (6 mg.kg(-1).d(-1); DS-diclofenac), rofecoxib (2 mg.kg(-1).d(-1); DS-rofecoxib), celecoxib (25 mg.kg(-1).d(-1); DS-celecoxib) or placebo (DS-placebo) was added to the chow. Blood pressure increased with sodium diet in the DS groups, which was more pronounced after diclofenac and rofecoxib treatment (P<0.005 versus DS-placebo) but was slightly decreased by celecoxib (P<0.001 versus DS-placebo). Sodium diet markedly reduced NO-mediated endothelium-dependent relaxations to acetylcholine (10(-10)-10(-5) mol/L) in aortic rings of untreated hypertensive rats (P<0.005 versus DR-placebo). Relaxation to acetylcholine improved after celecoxib (P<0.005 versus DS-placebo and DS-rofecoxib) but remained unchanged after rofecoxib and diclofenac treatment. Vasoconstriction after nitric oxide synthase inhibition, indicating basal NO release, with N-omega-nitro-L-arginine methyl ester (10(-4) mol/L) was blunted in DS rats (P<0.05 versus DR-placebo), normalized by celecoxib, but not affected by rofecoxib or diclofenac. Indicators of oxidative stress, 8-isoprostane levels, were elevated in untreated DS rats on 4% NaCl (6.55&PLUSMN;0.58 versus 3.65&PLUSMN;1.05 ng/mL, P<0.05) and normalized by celecoxib only (4.29+/-0.58 ng/mL).Conclusions-These data show that celecoxib but not rofecoxib or diclofenac improves endothelial dysfunction and reduces oxidative stress, thus pointing to differential effects of coxibs in salt-induced hypertension.