Molecular Pharmacological Studies on Effect of Docosahexaenoic Acid on Vascular Cell Functions

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The aim of the present project was to investigate the effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), n-3 polyunsaturated fatty acids, on protein and mRNA expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in cultured vascular smooth muscle cells isolated from 6-7 week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched normotensive Wistar Kyoto rats (WKY). The IL-1β-induced nitric oxide (NO) production and iNOS expression in cells of SHRSP were significantly lower than those in cells of WKY.Similarly, prostaglandins (PG)I2 production and COX-2 expression were significantly lower in cells of SHRSP than WKY, whereas there was no difference in the COX-1 expression. There were no significant differences in iNOS and COX-2 mRNA expressions between the two strains, suggesting that these protein expression may be impaired at post-transcriptional process in cells of SHRSP.DHA and EPA significantly enhanced the IL-1β-induced NO production in a concentration-dependent manner in cells of WKY, whereas had no effect in cells of SHRSP.DHA and EPA also significantly enhanced iNOS protein and mRNA expressions induced by IL-1β in cells of WKY but not in cells of SHRSP.DHA and EPA significantly increased COX-2, but not COX-1, protein expression induced by IL-1β in cells of WKY, but had no effect on COX-2 mRNA expression. These results suggest that the impairment of iNOS and COX-2 expressions in vascular smooth muscle cells may have relevance to the pathophysiology in SHRSP.These results further suggest that enhancement of NO and PGI2 productions by DHA may account for its beneficial effect on cardiovascular disorders.