Abstract 1108: Salt-Sensitive Hypertension in Mice Lacking Adiponectin
Background Patients with obesity exhibit increased susceptibility 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. In the current study, we investigated the association between adiponectin and hypertension.
Methods and Results: Adiponectin-deficient (KO) and wild-type (WT) mice were fed high salt diet (8% NaCl). Blood pressure and heart rate were measured using automatic sphygmomanometer at the tail artery or indwelling carotid artery catheters. Salt overload in adiponectin KO mice resulted in significant elevation of blood pressure without affecting heart rate or insulin sensitivity. Adenovirus-mediated adiponectin supplement lowered the blood pressure to the wild-type level. The salt-induced hypertension was associated with reduced mRNA levels of endothelial nitric oxide synthase (eNOS) and prostaglandin I2 synthase (PGIS) in aorta and low metabolite levels of eNOS and PGIS in plasma. Adiponectin supplementation increased the levels of these mRNAs. In obese diabetic KKAy mice, adiponectin supplementation significantly decreased blood pressure and increased plasma NO metabolites without affecting heart rate and insulin sensitivity. In tissue-cultured endothelial cells, adiponectin increased the mRNA and metabolites of eNOS and PGIS, which were abolished by an eNOS inhibitor, L-nitro-arginine-methyl-ester (L-NAME). L-NAME-induced elevation of blood pressure was not observed in the KO mice.
Conclusion Our results suggest that hypoadiponectinemia causes hypertension independent of insulin resistance, via the eNOS-PGIS pathway, and that adiponectin can be a novel therapeutic target against hypertension in the metabolic syndrome.