Exposure to Maternal Diabetes Mellitus Causes Renal Dopamine D1 Receptor Dysfunction and Hypertension in Adult Rat Offspring

被引:26
作者
Luo, Hao [1 ]
Chen, Caiyu [1 ]
Guo, Li [1 ]
Xu, Zaicheng [1 ]
Peng, Xiaoyu [1 ]
Wang, Xinquan [1 ]
Wang, Jialiang [1 ]
Wang, Na [1 ]
Li, Chuanwei [1 ]
Luo, Xiaoli [1 ]
Wang, Hongyong [1 ]
Jose, Pedro A. [4 ]
Fu, Chunjiang [1 ]
Huang, Yu [2 ,3 ]
Shi, Weibin [1 ]
Zeng, Chunyu [1 ]
机构
[1] Third Mil Med Univ, Chongqing Cardiovasc Clin Res Ctr, Chongqing Key Lab Hypertens, Dept Cardiol,Chongqing Inst Cardiol,Daping Hosp, Chongqing, Peoples R China
[2] Chinese Univ Hong Kong, Inst Vasc Med, Sha Tin, Hong Kong, Peoples R China
[3] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Sha Tin, Hong Kong, Peoples R China
[4] George Washington Univ, Sch Med & Hlth Sci, Div Renal Dis & Hypertens, Washington, DC 20052 USA
基金
美国国家科学基金会; 美国国家卫生研究院; 国家重点研发计划;
关键词
diabetes mellitus; dopamine; hypertension; oxidative stress; protein kinase C; PROTEIN-KINASE-C; OXIDATIVE STRESS; BLOOD-PRESSURE; PROXIMAL TUBULES; IN-UTERO; OLD RATS; D1; ACTIVATION; EXPRESSION; MOTHERS;
D O I
10.1161/HYPERTENSIONAHA.118.10908
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Epidemiological and experimental studies suggest that maternal diabetes mellitus programs hypertension that is associated with impaired sodium excretion in the adult offspring. However, the underlying mechanisms are not clear. Because dopamine receptor function is involved in the pathogenesis of hypertension, we hypothesized that impaired renal dopamine D-1 receptor function is also involved in the hypertension in offspring of maternal diabetes mellitus. Maternal diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (35 mg/kg) to pregnant Sprague-Dawley rats at day 0 of gestation. Compared with the offspring of mothers injected with citrate buffer (control mother offspring), the diabetic mother offspring (DMO) had increased systolic blood pressure and impaired D-1 receptor-mediated diuresis and natriuresis, accompanied by increased renal PKC (protein kinase C) expression and activity, GRK-2 (G protein-coupled receptor kinase-2) expression, D-1 receptor phosphorylation, D-1 receptor/Gs uncoupling, and loss of D-1 receptor-mediated inhibition of Na+-K+-ATPase activity in renal proximal tubule cells from DMO. Inhibition of PKC reduced the increased GRK-2 expression and normalized D-1 receptor function in primary cultures of renal proximal tubule cells from DMO. In addition, DMO, relative to control mother offspring, in vivo, had increased oxidative stress, indicated by decreased renal glutathione and increased renal malondialdehyde and urine 8-isoprostane. Normalization of oxidative stress with tempol also normalized the renal D-1 receptor phosphorylation, D-1 receptor-mediated diuresis and natriuresis, and blood pressure in DMO. Our present study indicates that maternal diabetes mellitus-programed hypertension in the offspring is caused by impaired renal D-1 receptor function because of oxidative stress that is mediated by increased PKC-GRK-2 activity.
引用
收藏
页码:962 / 970
页数:9
相关论文
共 57 条
[1]   Altered nephrogenesis due to maternal diabetes is associated with increased expression of IGF-II/mannose-6-phosphate receptor in the fetal kidney [J].
Amri, K ;
Freund, N ;
Van Huyen, JPD ;
Merlet-Bénichou, C ;
Lelièvre-Pégorier, M .
DIABETES, 2001, 50 (05) :1069-1075
[2]   Tempol reduces oxidative stress, improves insulin sensitivity, decreases renal dopamine D1 receptor hyperphosphorylation, and restores D1 receptor-G-protein coupling and function in obese Zucker rats [J].
Banday, AA ;
Marwaha, A ;
Tallam, LS ;
Lokhandwala, MF .
DIABETES, 2005, 54 (07) :2219-2226
[3]   Oxidative stress causes renal dopamine D1 receptor dysfunction and hypertension via mechanisms that involve nuclear factor-κB and protein kinase C [J].
Banday, Anees Ahmad ;
Fazili, Fatima Rizwan ;
Lokhandwala, Mustafa F. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2007, 18 (05) :1446-1457
[4]   Exposure in utero to maternal diabetes leads to glucose intolerance and high blood pressure with no major effects on lipid metabolism [J].
Blondeau, B. ;
Joly, B. ;
Perret, C. ;
Prince, S. ;
Bruneval, P. ;
Lelievre-Pegorier, M. ;
Fassot, C. ;
Van Huyen, J. -P. Duong .
DIABETES & METABOLISM, 2011, 37 (03) :245-251
[5]   Gestational Diabetes Mellitus and Future Cardiovascular Risk: An Update [J].
Burlina, S. ;
Dalfra, M. G. ;
Chilelli, N. C. ;
Lapolla, A. .
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY, 2016, 2016
[6]   Streptozotocin-Induced Maternal Hyperglycemia Increases the Expression of Antioxidant Enzymes and Mast Cell Number in Offspring Rat Ventral Prostate [J].
Camargo, Ana C. L. ;
Dos Santos, Sergio A. A. ;
Rinaldi, Jaqueline C. ;
Constantino, Flavia B. ;
Colombelli, Ketlin T. ;
Scarano, Wellerson R. ;
Felisbino, Sergio L. ;
Justulin, Luis A. .
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, 2017, 300 (02) :291-299
[7]   Renal dopamine system - Paracrine regulator of sodium homeostasis and blood pressure [J].
Carey, RM .
HYPERTENSION, 2001, 38 (03) :297-302
[8]   Catalase Prevents Maternal Diabetes-Induced Perinatal Programming via the Nrf2-HO-1 Defense System [J].
Chang, Shiao-Ying ;
Chen, Yun-Wen ;
Zhao, Xin-Ping ;
Chenier, Isabelle ;
Tran, Stella ;
Sauve, Alexandre ;
Ingelfinger, Julie R. ;
Zhang, Shao-Ling .
DIABETES, 2012, 61 (10) :2565-2574
[9]   INHIBITION OF NA+,K+-ATPASE IN RAT RENAL PROXIMAL TUBULES BY DOPAMINE INVOLVED DA-1 RECEPTOR ACTIVATION [J].
CHEN, CJ ;
LOKHANDWALA, MF .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1993, 347 (03) :289-295
[10]   Maternal diabetes programs hypertension and kidney injury in offspring [J].
Chen, Yun-Wen ;
Chenier, Isabelle ;
Tran, Stella ;
Scotcher, Michael ;
Chang, Shiao-Ying ;
Zhang, Shao-Ling .
PEDIATRIC NEPHROLOGY, 2010, 25 (07) :1319-1329