title: Fucoidan from Undaria pinnatifida prevents vascular dysfunction through PI3K/Akt/eNOS-dependent mechanisms in the l-NAME-induced hypertensive rat model.
abstract: Despite major scientific advances in its prevention, treatment and care, hypertension remains a serious condition that might lead to long-term complications such as heart disease and stroke. The great majority of forms of hypertension eventually result from an increased vasomotor tone activity that is regulated by endothelial NOS (eNOS) in vascular endothelium. Here, we examined the effect of fucoidan on eNOS activation in human umbilical vein endothelial cells (HUVECs). We also examined the effects of functional components of Undaria pinnatifida fucoidan on blood pressure and vascular function in eNOS inhibition-induced hypertensive rats in vivo. Our results suggest that fucoidan increased nitric oxide production by activating eNOS and Akt phosphorylation, which could be impaired by Akt or eNOS inhibitors. In the hypertensive rat model, treatment of fucoidan resulted in potent and persistent reduction of high blood pressure (BP) even after drug withdrawal. Our results showed that the mechanisms might involve protection against vascular structure damage, enhanced endothelium-independent vascular function and inhibition of abnormal proliferation of smooth muscle cells, which are mediated by the Akt-eNOS signaling pathway. Moreover, fucoidan treatment reduced the vascular inflammation and oxidative stress control caused by iNOS expression. Together, these results support a putative role of fucoidan in hypertension prevention and treatment.
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan University, Wuhan, China. 448481262@qq.com.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Zhike
authors.initials: Z
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Sang
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Niu
authors.forename: Qianying
authors.initials: Q
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Ding
authors.forename: Shanye
authors.initials: S
authors.lastname: Yin
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000517:prevention & control*; D007249:Inflammation / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044648:Undaria / Q000737:chemistry*
chemical_list: D016207:Cytokines; D011134:Polysaccharides; D009569:Nitric Oxide; C007789:fucoidan; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019869:Phosphatidylinositol 3-Kinases