P-645: Retinoid X receptor agonist improves endothelial dysfunction in spontaneously hypertensive rats

Abstract

Retinoid X receptors (RXRs) play a central role in regulating bile acid, cholesterol, fatty acid, steroid and xenobiotic metabolism and homeostasis. The present study is to investigate the effect of LG100364, a specific RXR agonist, on vascular reactivity in spontaneously hypertensive rats (SHR). 14-week-old SHR received either a specific RXR agonist (LG100364 at 20 mg/kg/day), or placebo for 8 weeks. At the end of the treatment period, the vascular reactivity of aortic rings was studied.

Treatment with LG100364 significantly augmented acetylcholine-induced relaxation in SHR (Rmax, 77 %±2% versus 58%±3%; P<0.001). Endothelium-independent relaxation induced by sodium nitroprusside was not different between the groups. The contractile response induced by the nitric oxide (NO) synthase inhibitor Nomega-nitro-l-arginine, an index of basal NO formation, was significantly higher in LG100364-treated rats compared with placebo-treated animals (P<0.01) . Our data suggest that activation of the RXR could enhance basal nitric oxide availability and ameliorates vascular relaxations in SHRs.

Endothelial Function, Retinoid X Receptor, Spontaneously Hypertensive Rat