title: Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats.
abstract: Endothelial dysfunction, characterized by impairment of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) bioavailability, has been implicated in diabetic cardiovascular pathogenesis. In this study, low-molecular-weight fucoidan (LMWF), which has multiple biological activities including anti-inflammatory and anti-oxidative properties, was investigated for its protective effect against endothelial dysfunction in Goto-Kakizaki type 2 diabetic rats. LMWF (50, 100, or 200 mg/kg/day) or probucol (100 mg/kg/day) were given to diabetic rats for 12 weeks. Basal blood pressure, acetylcholine- or flow-mediated relaxation of mesenteric and paw arteries, endothelium-dependent dilation of aorta, eNOS phosphorylation, and NO production were measured using laser Doppler flowmetry, force myograph, hematoxylin and eosin staining, western blot analysis, and an NO assay. We found that LMWF robustly ameliorated the basal hypertension and impairment of endothelium-dependent relaxation in the aorta, as well as mesenteric and paw arteries in diabetic rats. In addition, the reduction in eNOS phosphorylation at Ser1177, eNOS expression, and NO production because of diabetes were partially reversed by LMWF treatment. However, probucol, a lipid-modifying drug with antioxidant properties, displayed only mild effects. Moreover, LMWF induced, in a dose-dependent manner, endothelium-dependent vasodilation and eNOS phosphorylation at Ser1177 in normal aorta, and also promoted Ser1177 phosphorylation and NO synthesis in primary cultured vasoendothelial cells. Thus, these data demonstrate for the first time that fucoidan protects vasoendothelial function and reduces basal blood pressure in type 2 diabetes rats via, at least in part, preservation of eNOS function. Fucoidan is therefore a potential candidate drug for protection of endothelium in diabetic cardiovascular complications.
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing, PR China.
authors.forename: Wentong
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing, PR China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, Qingdao, PR China.
authors.forename: Quanbin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, Qingdao, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing, PR China.
authors.forename: Limin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing, PR China.
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing, PR China.
authors.forename: Chenyang
authors.initials: C
authors.lastname: Guo
authors.affiliation: Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Weidong
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Physiology, Capital Medical University, Beijing, PR China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing, PR China.
authors.forename: Dali
authors.initials: D
authors.lastname: Luo
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000494:pharmacology / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects; D048909:Diabetes Complications / Q000201:enzymology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects*; D006973:Hypertension / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008643:Mesentery / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000991:Antithrombins; D011134:Polysaccharides; D009569:Nitric Oxide; C007789:fucoidan; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat