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

Abstract

1. It is well documented that both acetylcholine‐evoked arterial relaxation and brachial artery flow‐mediated vasodilatation are blunted in hypercholesterolemic patients. However, there are no simple diagnostic methods to detect the pathology of blood vessels of patients.
2. In order 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 with a normal diet, a high cholesterol diet (HCD) or a HCD supplemented with simvastatin, a cholesterol lowering drug, (10 mg/kg/day p.o.), for 30 days. The serum total cholesterol level, serum NOS activity and acetylcholine‐induced vasorelaxation on isolated aorta were monitored at the end of the experiment.
3. Consumption of HCD for 30 days resulted in an elevation of serum total cholesterol, attenuated acetylcholine‐induced NO/endothelium‐dependent aortic relaxation and decreased NOS activity. A concomitant administration of simvastatin managed to lower the elevated cholesterol levels in blood with a complete reversal of the attenuated acetylcholine‐induced aortic relaxation and NOS activity in serum. An attempt was made to correlate the serum NOS activity and the magnitude of acetylcholine‐elicited vascular relaxation among the different groups. A positive correlation (r = 0.8329, P < 0.001, n = 30) between serum NOS activity and vascular relaxation was demonstrated for the first time.
4. 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 patients’ vascular systems.

© 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd