title: Adiponectin replenishment ameliorates obesity-related hypertension.
abstract: Patients with obesity are susceptible to hypertension. We have reported that the plasma adiponectin levels are decreased in obesity and that adiponectin has many defensive properties against obesity-related diseases, such as type 2 diabetes and coronary artery disease. The aim of this study was to determine the relationship between adiponectin and hypertension in mice. We measured blood pressure and heart rate directly by a catheter in the carotid artery and indirectly by automatic sphygmomanometer at the tail artery. Obese KKAy mice had significantly lower plasma adiponectin levels and higher systolic blood pressure than control C57BL/6J mice at 21 weeks of age. Adenovirus-delivered adiponectin significantly decreased blood pressure in KKAy mice. The direct role of adiponectin on blood pressure regulation under insulin resistance-free state was investigated in adiponectin-knockout (KO) mice. Adiponectin KO mice developed hypertension when maintained on a high-salt diet (8% NaCl) without insulin resistance. The hypertension of salt-fed adiponectin KO mice was associated with reduced mRNA levels of endothelial NO synthase (eNOS) and prostaglandin I(2) synthase in aorta and low metabolite levels of endothelial NO synthase and prostaglandin I(2) synthase in plasma. Adiponectin therapy lowered the elevated blood pressure and corrected the above mRNA levels to those of the wild type. Our results suggest that hypoadiponectinemia contributes to the development of obesity-related hypertension, at least in part, directly, in addition to its effect via insulin resistance, and that adiponectin therapy can be potentially useful for hypertension in patients with the metabolic syndrome.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ohashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kumada
authors.forename: Koichi
authors.initials: K
authors.lastname: Fujita
authors.forename: Aki
authors.initials: A
authors.lastname: Hiuge
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hibuse
authors.forename: Miwa
authors.initials: M
authors.lastname: Ryo
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishizawa
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Maeda
authors.forename: Rei
authors.initials: R
authors.lastname: Shibata
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D052242:Adiponectin / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D001794:Blood Pressure / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006973:Hypertension / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D007333:Insulin Resistance; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D009765:Obesity / Q000150:complications* / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage
chemical_list: D052242:Adiponectin; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D003577:Cytochrome P-450 Enzyme System; D052250:Nitric Oxide Synthase Type III; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D019331:NG-Nitroarginine Methyl Ester