Effect of chronic treatment with the inducible nitric oxide synthase inhibitor N-iminoethyl-L-lysine or with L-arginine on progression of coronary and aortic atherosclerosis in hypercholesterolemic rabbits

Citation
D. Behr-roussel et al., Effect of chronic treatment with the inducible nitric oxide synthase inhibitor N-iminoethyl-L-lysine or with L-arginine on progression of coronary and aortic atherosclerosis in hypercholesterolemic rabbits, CIRCULATION, 102(9), 2000, pp. 1033-1038
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
0009-7322 → ACNP
Volume
102
Issue
9
Year of publication
2000
Pages
1033 - 1038
Database
ISI
SICI code
0009-7322(20000829)102:9<1033:EOCTWT>2.0.ZU;2-#
Abstract
Background-We examined the implications of iNOS in atherosclerosis progress ion using the selective inducible NO synthase (iNOS) inhibitor N-iminoethyl -L-lysine (L-NIL) in hypercholesterolemic rabbits. Methods and Results-Nine rabbits were fed a 0.3% cholesterol diet for 24 we eks (Baseline group); 25 animals were maintained on the diet and treated fo r 12 extra weeks with L-NIL (5 mg . kg(-1) . d(-1), L-Nn group, n=8), vehic le (Saline group, n=9), or L-arginine (2.25%, L-Arg group, n=8), In abdomin al aortas of Saline rabbits, the lesions (53.7+/-5.7%, Baseline) increased to 75.0+/-5.0% (P<0.05) but remained unaltered in the L-NIL group (63.4+/-6 .6%). Similar results were obtained for the intima/media ratio in thoracic aortas. In coronary arteries, the intima/media ratio was comparable in Base line (0.68+/-0.18) and Saline (0.96+/-0.19) rabbits but decreased to 0.34+/ -0.19 (P<0.05) in L-NIL rabbits. L-Arginine had beneficial effects only in abdominal aortas. An increased thoracic aorta collagen content was found in Saline and L-Arg but not in L-NIL rabbits. In thoracic aortas of the Salin e group, acetylcholine caused modest relaxations that slightly increased by L-arginine but not by L-NIL. Relaxations to nitroglycerin were ameliorated by L-NIL. Conclusions-This is the first study showing that chronic treatment with an iNOS inhibitor, L-NIL, limits progression of preexisting atherosclerosis in hypercholesterolemic rabbits. Increased intimal collagen accumulation may participate in iNOS-induced atherosclerosis progression.