title: Impaired dopamine D1 receptor-mediated vasorelaxation of mesenteric arteries in obese Zucker rats.
abstract: BACKGROUND
  Obesity plays an important role in the pathogenesis of hypertension. Renal dopamine D1-like receptor-mediated diuresis and natriuresis are impaired in the obese Zucker rat, an obesity-related hypertensive rat model. The role of arterial D1 receptors in the hypertension of obese Zucker rats is not clear.
  
  
  METHODS
  Plasma glucose and insulin concentrations and blood pressure were measured. The vasodilatory response of isolated mesenteric arteries was evaluated using a small vessel myograph. The expression and phosphorylation of D1 receptors were quantified by co-immunoprecipitation and immunoblotting To determine the effect of hyperinsulinemia and hyperglycemia on the function of the arterial D1 receptor, we studied obese Zucker rats (six to eight-weeks old) fed (6 weeks) vehicle or rosiglitazone, an insulin sensitizer (10 mg/kg per day) and lean Zucker rats (eight to ten-weeks old), fed high-fat diet to induce hyperinsulinemia or injected intraperitoneally with streptomycin (STZ) to induce hyperglycemia.
  
  
  RESULTS
  In obese Zucker rats, the vasorelaxant effect of D1-like receptors was impaired that could be ascribed to decreased arterial D1 receptor expression and increased D1 receptor phosphorylation. In these obese rats, rosiglitazone normalized the arterial D1 receptor expression and phosphorylation and improved the D1-like receptor-mediated vasorelaxation. We also found that D1 receptor-dependent vasorelaxation was decreased in lean Zucker rats with hyperinsulinemia or hyperglycemia but the D1 receptor dysfunction was greater in the former than in the latter group. The ability of insulin and glucose to decrease D1 receptor expression and increase its phosphorylation were confirmed in studies of rat aortic smooth muscle cells.
  
  
  CONCLUSIONS
  Both hyperinsulinemia and hyperglycemia caused D1 receptor dysfunction by decreasing arterial D1 receptor expression and increasing D1 receptor phosphorylation. Impaired D1 receptor-mediated vasorelaxation is involved in the pathogenesis of obesity-related hypertension.
authors.forename: Jinjuan
authors.initials: J
authors.lastname: Fu
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.forename: Hongyong
authors.initials: H
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Yukai
authors.initials: Y
authors.lastname: Liu
authors.forename: Xingjian
authors.initials: X
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Cai
authors.forename: Weiwei
authors.initials: W
authors.lastname: Guan
authors.forename: Di
authors.initials: D
authors.lastname: Yang
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P,R, China. zhoulin@mail.tmmu.com.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000818:Animals; D008297:Male; D008638:Mesenteric Arteries / Q000473:pathology / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D011924:Rats, Zucker; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D017447:Receptors, Dopamine D1