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

ABSTRACT: 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 D1 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 D1 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, D1 receptor phosphorylation, D1 receptor/G?s uncoupling, and loss of D1 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 D1 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 D1 receptor phosphorylation, D1 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 D1 receptor function because of oxidative stress that is mediated by increased PKC-GRK-2 activity.

SUBMITTER: Luo H

PROVIDER: S-EPMC6207228 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Exposure to Maternal Diabetes Mellitus Causes Renal Dopamine D<sub>1</sub> Receptor Dysfunction and Hypertension in Adult Rat Offspring.

Luo Hao H Chen Caiyu C Guo Li L Xu Zaicheng Z Peng Xiaoyu X Wang Xinquan X Wang Jialiang J Wang Na N Li Chuanwei C Luo Xiaoli X Wang Hongyong H Jose Pedro A PA Fu Chunjiang C Huang Yu Y Shi Weibin W Zeng Chunyu C

Hypertension (Dallas, Tex. : 1979) 20181001 4

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<sub>1</sub> receptor function is also involved in the hypertension in offspring of maternal diabetes mellitus. Maternal diabetes mellitus was ...[more]

PMID: 30354705

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Dataset Information

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

Publications

Exposure to Maternal Diabetes Mellitus Causes Renal Dopamine D<sub>1</sub> Receptor Dysfunction and Hypertension in Adult Rat Offspring.

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