Linoleic acid modulates vascular reactivity, alters cyclooxygenase-2-derived products, and promotes eutrophic remodeling in small mesenteric arteries of normotensive rats

Linoleic acid (LA) is a polyunsaturated fatty acid with essential roles in cardiovascular regulation. Despite its known vascular effects, its impact on mesenteric resistance arteries (MRA) in normotensive models remains unclear. This study aimed to determine whether LA induces functional and structural changes in MRA of normotensive rats by modulating endothelial mechanisms. We hypothesized that LA treatment reduces vasoconstrictor reactivity and promotes vascular remodeling via enhanced nitric oxide (NO) bioavailability. Male Wistar rats were treated with LA (15 mg/kg) or vehicle for 15 days. LA did not alter blood pressure, mechanical parameters, or collagen and elastin levels in the MRA, but it increased both external and internal diameters of the vessels, reducing the wall-to-lumen ratio. LA decreased the contractile response to phenylephrine, without affecting responses to acetylcholine or sodium nitroprusside. l-NAME (100 µM) enhanced vasoconstriction to a greater extent in the LA-treated group, associated with increased nitric oxide (NO) bioavailability, independent of inducible NO synthase (iNOS) and phosphatidylinositol 3- kinase (PI3K). The NADPH oxidase pathway had a lesser impact on vasoconstriction in the LA group, although the superoxide anion scavenger tiron (1 mM) and the production of reactive oxygen species showed similar results. Inhibition of ciclooxigenase (COX) and cytochrome-P450 (CYP450) attenuated vascular reactivity in the LA group, with greater involvement of COX-2-derived products. While SC 19220 (EP1 receptor antagonist, 10 µM) reduced vasoconstrictor responses to phenylephrine only in MRA from the LA-treated group, SQ 29.548 (TP receptor antagonist, 1 µM) reduced responses only in controls. In conclusion, LA reduces vasoconstriction, increases NO bioavailability and decreases NADPH oxidase participation associated with alterations in CYP450 and COX-2-derived products.