Abstract MP54: Pro-resolving Lipid Mediators Ameliorate Endothelium Dysfunction In Arteries From Hypertensive Rats

Abstract

Resolution of inflammation is an active phenomenon to switch off the inflammatory processes andfacilitate the return to homeostasis. Increasing the levels of pro-resolving lipid mediators topromote the resolution of inflammation is emerging as a novel therapeutic approach. Arachidonicacid (AA) and docosahexaenoic acid (DHA) are substrates to produce the pro-resolving lipidmediators lipoxin A4 (LXA4) and resolvin D1 (RvD1), respectively. However, it is unknown if thesemediators can ameliorate dysfunction in arteries from hypertensive animals. Therefore, wehypothesized that pro-resolving lipid mediators decrease acetylcholine-induced contractions inarteries from spontaneously hypertensive rats (SHR). Mesenteric resistance arteries from maleSHR and Wistar Kyoto (WKY) (14-weeks old, n=6-8) were used for vascular function via wiremyograph. MRA were incubated with either RvD1 or LXA4 (10 nM, 1 hour) or vehicle prior toconcentration response curves to acetylcholine or phenylephrine (1 nM - 3 μM). We alsoperformed lipidomic analysis on plasma from WKY and SHR. As expected, low concentrations (≤100 nM) of acetylcholine induced relaxation in arteries from both groups, however highconcentrations (≥ 1 μM) of acetylcholine induced contraction in arteries from SHR, but not in WKY[Relaxation to acetylcholine [Area Under the curve (AUC)]: WKY: 396.6 ± 17.7 vs. SHR-control:296.0 ± 26.7*, t-test *vs. WKY, p=0.03). Treatment with the mediators did not change relaxationin arteries from WKY (AUC: Vehicle: 396.6 ±17.7 vs. RvD1: 402.8 ± 18.0; LXA4: 399.0 ± 18.4,p>0.05). However, incubation with RvD1 or LXA4 reduced acetylcholine induced-contraction inarteries from SHR (AUC: Vehicle: 296.0 ± 26.7 vs. RvD1: 372.5 ± 18.5*; LXA4: 376.8 ± 23.6*, t-test *vs. vehicle, p<0.05). Lipidomic analysis showed that precursors for pro-resolving lipidmediators are decreased in SHR [DHA (pmol/mL): WKY: 5637.5 ± 275.3 vs. SHR: 4509.2 ±453.9*, AA: WKY:16018.3 ± 351.3 vs. SHR: 13928.5 ± 959.5 *vs. WKY, p<0.05]. Overall, theseresults suggest that resolution of inflammation and the pro-resolving lipid mediators, RvD1 orLXA4, may be used as a new therapeutic tool to improve vascular function in hypertension.