Adiponectin opposes endothelin-1-mediated vasoconstriction in the perfused rat hindlimb

作者：Bussey Carol T; Kolka Cathryn M; Rattigan Stephen; Richards Stephen M^*

来源：American Journal of Physiology - Heart and Circulatory Physiology, 2011, 301(1): H79-H86.

DOI：10.1152/ajpheart.00864.2010

• skeletal muscle
• vasculature
• vasodilation
• glucose metabolism

Bussey CT, Kolka CM, Rattigan S, Richards SM. Adiponectin opposes endothelin-1-mediated vasoconstriction in the perfused rat hindlimb. Am J Physiol Heart Circ Physiol 301: H79-H86, 2011. First published April 22, 2011; doi:10.1152/ajpheart.00864.2010.-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 mu g/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.

• 出版日期2011-7