title: Adiponectin opposes endothelin-1-mediated vasoconstriction in the perfused rat hindlimb.
abstract: Recent studies have shown that adiponectin is able to increase nitric oxide (NO) production by the endothelium and relax preconstricted isolated aortic rings, suggesting that adiponectin may act as a vasodilator. Endothelin-1 (ET-1) is a potent vasoconstrictor, elevated levels of which are associated with obesity, type 2 diabetes, hypertension, and cardiovascular disease. We hypothesized that adiponectin has NO-dependent vascular actions opposing the vasoconstrictor actions of ET-1. We studied the vascular and metabolic effects of a physiological concentration of adiponectin (6.5 μg/ml) on hooded Wistar rats in the constant-flow pump-perfused rat hindlimb. Adiponectin alone had no observable vascular activity; however, adiponectin pretreatment and coinfusion inhibited the increase in perfusion pressure and associated metabolic stimulation caused by low-dose (1 nM) ET-1. Adiponectin was not able to oppose vasoconstriction when infusion was commenced after ET-1. This is in contrast to the NO donor sodium nitroprusside, which significantly reduced the pressure due to established ET-1 vasoconstriction, suggesting dissociation of the actions of adiponectin and NO. In addition, adiponectin had no effect on vasoconstriction caused by either high-dose (20 nM) ET-1 or low-dose (50 nM) norepinephrine. Our findings suggest that adiponectin has specific, apparently NO-independent, vascular activity to oppose the vasoconstrictor effects of ET-1. The hemodynamic actions of adiponectin may be an important aspect of its insulin-sensitizing ability by regulating access of insulin and glucose to myocytes. Imbalance in the relationship between adiponectin and ET-1 in obesity may contribute to the development of insulin resistance and cardiovascular disease.
authors.affiliation: Menzies Research Institute, Medical Science 1 Bldg., Private Bag 23, Hobart, Tasmania, Australia 7000.
authors.forename: Carol T
authors.initials: CT
authors.lastname: Bussey
authors.forename: Cathryn M
authors.initials: CM
authors.lastname: Kolka
authors.forename: Stephen
authors.initials: S
authors.lastname: Rattigan
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Richards
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D018076:DNA, Complementary; D019332:Endothelin-1; D007004:Hypoglycemic Agents; D007328:Insulin; D020030:Nitric Oxide Donors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide; D005947:Glucose; D009638:Norepinephrine