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Open Access Original investigation

Impaired dopamine D1 receptor-mediated vasorelaxation of mesenteric arteries in obese Zucker rats

Jinjuan Fu12, Yu Han12, Hongyong Wang12, Zhen Wang12, Yukai Liu12, Xingjian Chen12, Yue Cai12, Weiwei Guan12, Di Yang12, Laureano D Asico3, Lin Zhou12*, Pedro A Jose34 and Chunyu Zeng12*

Author Affiliations

1 Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China

2 Chongqing Institute of Cardiology, Chongqing, P.R. China

3 Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

4 Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA

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Cardiovascular Diabetology 2014, 13:50  doi:10.1186/1475-2840-13-50

Published: 22 February 2014

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.

Keywords:
Dopamine D1 receptor; Vasorelaxation; Hyperinsulinemia; Hyperglycemia; Obesity-related hypertension; Obese Zucker rats