CALL FOR PAPERS Metabolic Syndrome Enhanced role for RhoA-associated kinase in adrenergic-mediated vasoconstriction in gracilis arteries from obese Zucker rats

Naik, Jay S., Lusha Xiang, and Robert L. Hester. Enhanced role for RhoA-associated kinase in adrenergic-mediated vasoconstriction in gracilis arteries from obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 290: R154–R161, 2006. First published September 1, 2005; doi:10.1152/ajpregu.00245.2005.—Obesity, insulin resistance, dyslipidemia, and hypertension are components of the pathophysiological state known as metabolic syndrome. Adrenergic vasoconstriction is mediated through increases in cytosolic Ca and the myofilaments’ sensitivity to Ca . In many pathophysiological states, there is an enhanced role for Rho kinase (ROK)-mediated increases in Ca sensitivity of the contractile apparatus. Thus we hypothesized that there is a greater role for ROK-mediated increases in Ca sensitivity in 1-adrenergic vasoconstriction in arteries from obese Zucker (OZ) rats. Therefore, small gracilis muscle arteries from 11to 12-wk-old and 16to 18-wk-old lean and OZ rats were isolated, cannulated, and pressurized to 75 mmHg. For some experiments, vessels were loaded with fura 2-AM. Changes in luminal diameter and vessel wall Ca concentration ([Ca ]) were measured in response to phenylephrine (PE), the thromboxane mimetic U-46619, and KCl. 1-Adrenergic vasoconstriction was similar between 11to 12-wk-old lean and obese animals and greater in older obese animals compared with controls. PE-induced increases in vascular smooth muscle cell [Ca ] were blunted in OZ animals compared with lean controls in both age groups of animals. KCl and U-46619 elicited similar vasoconstriction and vascular smooth muscle cell [Ca ] in both groups. ROK inhibition attenuated PE vasoconstriction to a greater degree in arteries from 11to 12-wk-old OZ rats compared with lean animals; ROK inhibition in arteries from older rats right shifted both concentration-response curves to the same point. Total RhoA and ROK protein expressions were similar between groups. These results suggest an enhanced role for the ROK pathway in 1-adrenergic vasoconstriction in metabolic syndrome.