Endothelial nitric oxide synthase activity in aorta of normocholesterolemic rabbits: regional variation and the effect of estrogen

Objective: Several animal studies suggest that nitric oxide (NO) produced b y the endothelium attenuates arterial cholesterol accumulation. In the pres ent study we have asked the following questions: (1) is the regional variat ion in aortic cholesterol accumulation in hypercholesterolemic rabbits prec eded by a regional variation in endothelial NO synthase (eNOS) activity in normocholesterolemic rabbits, and (2) is the antiatherogenic effect of estr ogen in hypercholesterolemic rabbits preceded by a higher eNOS activity in normocholesterolemic rabbits. Methods: The eNOS activity was determined by conversion of C-14-L-arginine to C-14-L-citrulline in freshly isolated endo thelial cells of aorta in normocholesterolemic rabbits. In the regional var iation study, 16 male and eight female rabbits were used. In the estrogen s tudy, ovariectomized female rabbits were subcutaneously injected three time s weekly with either 17 beta-estradiol (n=7) or vehicle (n=7) for 18 weeks. Results: In the regional variation study, the atherosclerosis prone aortic arch showed a significant lower eNOS activity than the more resistant abdo minal aorta in both male (P<0.0001) and female (P<0.05) rabbits. In the est rogen study, the eNOS activity in the aortic arch and upper thoracic aorta was significantly higher in the estrogen than in the vehicle rabbits (P<0.0 5). In the lower thoracic aorta, however, the eNOS activity was the same. C onclusion: The findings suggest that a high NO production in the luminal en dothelium of the arterial wall precedes a low cholesterol accumulation duri ng a subsequent period of hypercholesterolemia. (C) 2000 Elsevier Science B .V. All rights reserved.