Adiponectin replenishment ameliorates obesity-related hypertension.
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.
Ohashi
Koji
K
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Kihara
Shinji
S
Ouchi
Noriyuki
N
Kumada
Masahiro
M
Fujita
Koichi
K
Hiuge
Aki
A
Hibuse
Toshiyuki
T
Ryo
Miwa
M
Nishizawa
Hitoshi
H
Maeda
Norikazu
N
Maeda
Kazuhisa
K
Shibata
Rei
R
Walsh
Kenneth
K
Funahashi
Tohru
T
Shimomura
Iichiro
I
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
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