Is it too early to declare nitric oxide synthase activity as a novel predictor of stiff vessel walls in atherosclerosis?

Abstract

We would like to make the following comments regarding the recent communication Serum nitric oxide synthase activity is a novel predictor of impaired vasorelaxation in rats, published in a recent issue of the Journal. 1 First, although the authors delicately investigated the links between lower serum nitric oxide synthase (NOS) activity, high cholesterol and decreased relaxation of isolated aortic rings, the results reported by the authors are not surprising. It has been reported previously that, in cultured neuroblastoma cells, mevastatin and serum rapidly increase neuronal NOS expression. 2 Furthermore, an important role has been demonstrated for endothelial (e) NOS expression in protecting vessel walls against atherosclerosis in hypercholesterolaemic rabbits, without concomitant decreases in inducible NOS. 3 In yet another study, the effects of a high-cholesterol diet on the oxidant/anti-oxidant status and NOS activity were evaluated in rat erythrocytes. 4 In that study, following the feeding of a high-cholesterol diet, the authors found increases in the indices of oxidative stress (malondialdehyde, xanthine oxidase) associated with reductions in NOS activity. 4 Together, the findings of these studies highlight the fact that atherosclerosis is a chronic and complicated process and that although vessel elasticity is an important index that can be used to predict the outcome of atherosclerosis, many factors can affect and regulate serum NOS activity. For example, statins are known to enhance eNOS activity, but they do not induce increased expression of eNOS mRNA or protein in platelets.Thus, it is too early to declare that decreased NOS activity can be used as a reliable biomarker of impaired vessel relaxation in atherosclerosis.