Impaired dopamine D1 receptor-mediated vasorelaxation of mesenteric arteries in obese Zucker rats.
Impaired dopamine D1 receptor-mediated vasorelaxation of mesenteric arteries in obese Zucker rats.
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DOI：
10.1186/1475-2840-13-50
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发表时间：
2014-02-22
影响因子：
9.3
通讯作者：
Zeng C
中科院分区：
文献类型：
--
作者：
Fu J;Han Y;Wang H;Wang Z;Liu Y;Chen X;Cai Y;Guan W;Yang D;Asico LD;Zhou L;Jose PA;Zeng C
肥胖在高血压的发病机制中起重要作用。肥胖Zucker大鼠（一种肥胖相关高血压大鼠模型）肾多巴胺D1样受体介导的利尿和尿钠排泄受损。动脉D1受体在肥胖Zucker大鼠高血压中的作用尚不清楚。测量血糖和胰岛素浓度以及血压。使用小血管肌电描记器评价离体肠系膜动脉的血管舒张反应。通过免疫共沉淀和免疫印迹定量D1受体的表达和磷酸化。为了确定高胰岛素血症和高血糖对动脉D1受体功能的影响，我们研究了肥胖Zucker大鼠（6 - 8周龄）喂食（6周）溶媒或胰岛素增敏剂罗格列酮（10 mg/kg/天）和瘦Zucker大鼠（8 - 10周龄），喂食高脂肪饲料以诱导高胰岛素血症或腹腔注射链霉素（STZ）以诱导高血糖症。在肥胖Zucker大鼠中，D1样受体的血管舒张作用受损，这可能归因于动脉D1受体表达减少和D1受体磷酸化增加。在这些肥胖大鼠中，罗格列酮使动脉D1受体表达和磷酸化正常化，并改善D1样受体介导的血管舒张。我们还发现，D1受体依赖性血管舒张功能下降，在瘦Zucker大鼠高胰岛素血症或高血糖症，但D1受体功能障碍是在前者比后者组更大。在大鼠主动脉平滑肌细胞的研究中证实了胰岛素和葡萄糖降低D1受体表达并增加其磷酸化的能力。高胰岛素血症和高血糖症均通过降低动脉D1受体表达和增加D1受体磷酸化而引起D1受体功能障碍。D1受体介导的血管舒张功能受损参与肥胖相关高血压的发病机制。
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. 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. 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. 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.
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影响因子：
3
作者：
de Vries, PAM;de Zeeuw, D;Navis, G
通讯作者：
Navis, G
影响因子：
6.9
作者：
Ebenezer, Philip J.;Mariappan, Nithya;Elks, Carrie M.;Haque, Masudul;Francis, Joseph
通讯作者：
Francis, Joseph
影响因子：
4.7
作者：
Baladi MG;Daws LC;France CP
通讯作者：
France CP
DOI：
10.1152/ajpregu.00178.2008
发表时间：
2008-06-01
影响因子：
2.8
作者：
Henriksen, Erik J.;Teachey, Mary K.;Beneze, Alan N.
通讯作者：
Beneze, Alan N.
影响因子：
9.3
作者：
Leguisamo NM;Lehnen AM;Machado UF;Okamoto MM;Markoski MM;Pinto GH;Schaan BD
通讯作者：
Schaan BD