Serum nitric oxide synthase activity is a novel predictor of impaired vasorelaxation in rats

Abstract

Summary It is well documented that both acetylcholine (ACh)‐evoked arterial relaxation and brachial artery flow‐mediated vasodilatation are blunted in hypercholesterolaemic patients. However, there are no simple diagnostic methods to detect the pathology of blood vessels of patients. To establish the use of serum nitric oxide synthase (NOS) activity as a diagnostic parameter for impaired vasorelaxation, animals with different levels of vascular healthiness were made by feeding Sprague–Dawley rats a normal diet, a high‐cholesterol diet (HCD) or an HCD supplemented with 10 mg/kg per day, p.o., simvastatin, a cholesterol‐lowering drug, for 30 days. Serum total cholesterol levels, serum NOS activity and ACh‐induced vasorelaxation of the isolated aorta were determined at the end of the experiment. Consumption of HCD for 30 days resulted in an increase in serum total cholesterol, attenuated ACh‐induced nitric oxide/endothelium‐dependent aortic relaxation and decreased NOS activity. Concomitant administration of simvastatin lowered the elevated blood cholesterol levels with complete reversal of the attenuated ACh‐induced aortic relaxation and serum NOS activity. An attempt was made to correlate serum NOS activity and the magnitude of ACh‐elicited vascular relaxation among the different groups. A positive correlation (r = 0.8329; P < 0.001; n = 30) was found between serum NOS activity and vascular relaxation. This finding is a good foundation for the development of a simple and low‐cost alternative for diagnosing vascular diseases and evaluating the effectiveness of drugs on the vascular system in patients.

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

“…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.…”

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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.

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A Review of the Pharmacological Effects of Piceatannol on Cardiovascular Diseases

“…Elevated plasma cholesterol and glucose-induced oxidative stress are common causes of endothelial dysfunction with decreasing NO production in the endothelium (Chan et al, 2012;Seto et al, 2009). A study found that piceatannol-3'-O-beta-D-glucopyranoside (PG) could inhibit arginase (a regulator of the eNOS) activity, increase NO production, and decrease reactive oxygen species generation in thoracic aorta of apolipoprotein E-null mice (ApoEÀ/À) fed with high-cholesterol diet (HCD).…”

A Review of the Phytochemistry and Pharmacological Activities of Raphani Semen

“…Through decreasing serum malondialdehyde content and enhancing superoxide dismutase activity in vivo , Raphani Semen alkaloids are believed to have good cardiovascular protective effects from oxidative damage. In addition, choline, a metabolite from the degradation of sinapine in Raphani Semen extract in the digestive system, might activate the NO-NOS system [90], thereby increasing the synthesis of NO and resulting in vasodilation [9]. However, whether the anti-hypertensive effect of water-soluble alkaloids from Raphani Semen resulted from the increase in NO availability by directly enhancing NO production (stimulation of NOS activity), by indirectly reducing NO degradation (antioxidant properties), or by both pathways was currently unknown and warranted further investigations.…”