972 RELAXATION EFFECT OF ALL-TRANS RETINOIC ACID VIA NO-SGC-CGMP PATHWAY AND CALCIUM ACTIVATED POTASSIUM CHANNELS IN RAT MESENTERIC ARTERY

Abstract

Background: Intraperitoneal injection of all-trans retinoic acid (ATRA) results in a reduction of blood pressure in spontaneously hypertensive rats. However, the mechanisms are not clear. We hypothesized that ATRA may relax resistance arteries. Results: In this study, we found that ATRA relaxes preconstricted mesenteric arterial rings induced by phenylephrine (PhE) which is abrogated by removal of the endothelium. Pretreatment of endothelium-intact arterial rings with an inhibitor of endothelial nitric oxide synthase (eNOS), L-NAME, or an inhibitor of soluble guanylyl cyclase (sGC), ODQ, reduced the vasorelaxant effect of ATRA. Incubation of mesenteric arterial rings with ATRA increased the production of NO and cyclic guanosine monophosphate (cGMP) which was blocked by L-NAME. The vasorelaxant effect of ATRA was markedly attenuated in the presence of a small- (apamin) and large-conductance calcium-activated potassium channel blocker (charybdotoxin), but not by an inhibitor of voltage dependent potassium channel (4-aminopynidine), or an inhibitor of ATP sensitive potassium channel (glibenclamide). Activation of retinoic acid receptors (RAR) with CH55 or retinoic X receptors (RXR) with LGD1069 induced the vasorelaxation of mesenteric arterial rings preconstricted by PhE. The RAR (BMS493) and RXR (UVI3003) antagonists blocked the ATRA-induced vasorelaxation. Conclusions: We conclude that ATRA relaxes resistance vessels, via both RAR and RXR receptors that is mediated by the endothelium-dependent NO-cGMP pathway.