Abstract 18322: A Ligand of Scavenger Receptor Class A Causes Vascular Relaxation Through an Activation of Endothelial Nitric Oxide Synthase in Rat Aorta
The class A scavenger receptor (SR-A) are implicated in the development and progression of atherosclerosis. In addition to modified low-density lipoprotein, a diverse group of polyanionic compounds are listed as ligands for SR-A. Fucoidan is a natural sulfated polysaccharide obtained from brown marine algae and is a well-defined nonlipoprotein ligand for SR-A. It is attracting attentions due to its wide variety of biological effects including anticoagulant and antithrombotic activities, however, its effects on vascular tone are not fully elucidated. In the present study, we examined the effects of acute administration of fucoidan (10 μg/ml to 1 mg/ml) to isolated rat thoracic aorta (RA) and explored the mechanism(s) of action. Fucoidan caused RA relaxation in a dose-dependent manner, and this relaxation was significantly attenuated by the removal of endothelium; 88.4±5.8 % (mean±SEM, n=17) in the presence and 24.6±7.5 % (n=10) in the absence of endothelium at 1 mg/ml fucoidan. Fucoidan-induced relaxation was also significantly inhibited by both a nitric oxide (NO) synthase (NOS) inhibitor 300 μM L-NAME (N(G)-nitro-L-arginine methyl ester, 37.8±13.1 %, n=6) and a selective inhibitor of soluble guanylyl cyclase 10 μM ODQ (1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one, 33.0±5.6 %, n=8), but not affected by a cyclooxygenase inhibitor 10 μM indomethacin or various kinds of K+ channel blockers including 10 mM tetraethylammonium, 10 μM glibenclamide and a combination of 0.1 μM apamin plus 0.1 μM charybdotoxin which is thought to block endothelium-derived hyperpolarizing factor-mediated reaction. NO production measured by Griess method in cultured human aortic endothelial cells (HAEC) was dose-dependently increased by fucoidan. Western blotting analyses revealed that fucoidan phosphorylated endothelial NOS (eNOS) at Ser-1177 and also phosphorylated protein kinase Akt at Ser-473 in a dose-dependent manner in HAEC, indicating an activation of eNOS. These results indicate that fucoidan, a ligand of SR-A, causes vascular relaxation through an endothelium-dependent and, at least in part, NO/cGMP-mediated mechanism through an activation of eNOS.
- Vasodilator agents
- Endothelium-derived relaxing factor
- Nitric oxide synthase
- Receptor-mediated signaling
- © 2012 by American Heart Association, Inc.