Dopamine, hypertension and obesity

Contreras, Freddy; Fouillioux, Christian; Bolívar, A; Simonovis, Nelson; Hernández-Hernández, Rafael; Armas-Hernández, María José; Velasco, Manuel

doi:10.1038/sj.jhh.1001334

Cited by 45 publications

(16 citation statements)

References 47 publications

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“…A decreased renal production of dopamine, dopamine receptor density, and/or an uncoupling of the dopamine receptors from their G protein effector complexes has been described in essential hypertension (6,42) and in the metabolic syndrome (11,33). However, endogenous renal dopamine production is normal or even increased in obese humans (46), monkeys (43), and rats (39).…”

Section: Discussionmentioning

confidence: 99%

Reduction of renal dopamine receptor expression in obese Zucker rats: role of sex and angiotensin II

Wang

José

et al. 2010

American Journal of Physiology-Renal Physiology

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Ecelbarger CM. Reduction of renal dopamine receptor expression in obese Zucker rats: role of sex and angiotensin II. Am J Physiol Renal Physiol 299: F1164-F1170, 2010. First published September 1, 2010 doi:10.1152/ajprenal.00604.2009.-Dopamine produced by renal proximal tubules increases sodium excretion via a decrease in renal sodium reabsorption. Dopamine natriuresis is impaired in obese Zucker rats; however, the mechanism is not fully understood. To test the hypothesis that renal expression of one or more of the subtypes are altered in these rats, we measured whole kidney protein levels by immunoblotting of D1-like (D1R and D5R) and D2-like (D2R, D3R, and D4R) dopamine receptors in both male and female obese and lean Zucker rats. In obese males on 1% NaCl diet, D1R, D2R, D4R, and D5R were decreased, while D3R was increased, relative to lean rats. Under a 4% NaCl diet, D2R and D3R levels in obese rats were restored to lean levels. 4% NaCl diet reduced D5R in both body types, relative to 1% NaCl diet. Female rats had higher expression of D1R and D3R than did male; however, the sex difference for D1R was markedly blunted in obese rats. In obese rats, dietary candesartan (angiotensin II type 1 receptor blocker) normalized downregulated D1R and D2R, but either decreased (D3R), did not affect (D4R), or further downregulated (D5R) the other subtypes. Candesartan also decreased D4R in lean rats. In summary, reduced renal protein levels of D1R, D2R, D4R, and D5R in obese Zucker rats could induce salt sensitivity and elevate blood pressure. Increased angiotensin II type 1 receptor activity may be mechanistically involved in the decreased expression of D1R and D2R in obese rats. Finally, reduced D1R and D3R in male rats may contribute to sex differences in blood pressure.

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Section: Discussionmentioning

confidence: 99%

Reduction of renal dopamine receptor expression in obese Zucker rats: role of sex and angiotensin II

Wang

José

et al. 2010

American Journal of Physiology-Renal Physiology

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“…Although this is a well-recognized mechanism for D1R desensitization, there are reports that animal models which exhibit oxidative stress and moderate hypertension and fail to produce natriuresis in response to dopamine, a decrease in receptor number alone could contribute to D1R dysfunction. 16–18 To identify the role and mechanism of D1R down-regulation, we focused on redox sensitive transcription factors which possess putative binding affinity for D1R promoter. In here we found that BSO reduced both the D1R mRNA level and membrane receptor numbers suggesting a transcriptional suppression.…”

Section: Discussionmentioning

confidence: 99%

“…12 However, there are reports which show that receptor dysfunction due to G protein uncoupling is caused by a decrease in D1R expression. 16–18 Therefore, this study was undertaken to investigate the mechanism of D1R down-regulation during oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Regulation of Renal Dopamine D1 Receptor Function During Oxidative Stress

Banday

Lokhandwala

2015

Hypertension

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There exists a strong link between oxidative stress, renal dopaminergic system and hypertension. It is reported that reactive oxygen species attenuate renal proximal tubular dopamine receptor (D1R) function which disrupts sodium regulation and leads to hypertension. The mechanisms for renal D1R dysfunction however are not clear. We investigated the role of redox sensitive transcription factors AP1 and SP3 in transcriptional suppression of D1R gene and subsequent D1R signaling. Human kidney (HK2) proximal tubular cells were treated with a pro-oxidant L-buthionine sulfoximine (BSO) with and without an antioxidant tempol. In HK2 cells BSO caused oxidative stress and reduced D1R mRNA and membrane receptor expression. Incubation of HK2 cells with SKF38393, a D1R agonist, caused a concentration dependent inhibition of Na/K-ATPase. However, SKF38393 failed to inhibit Na/K-ATPase in BSO-treated cells. BSO increased AP1 and SP3 nuclear expression. Transfection with AP1 or SP3 specific siRNA abolished BSO-induced D1R down-regulation. Treatment of rats with BSO for 4 weeks increased oxidative stress and SP3—AP1 expression and reduced D1R numbers in renal proximal tubules. These rats exhibited high blood pressure and SKF38393 failed to inhibit proximal tubular Na/K-ATPase activity. Control rats were kept on tap water. Tempol per se had no effect on D1R expression or other signaling molecules but prevented BSO-induced oxidative stress, SP3—AP1 up-regulation and D1R dysfunction in both HK2 cells and rats. These data shows that oxidative stress via AP1—SP3 activation suppresses D1R transcription and function. Tempol mitigates oxidative stress, blocks AP1—SP3 activation and prevents D1R dysfunction and hypertension.

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“…Dopamine (DA) is essential in sodium balance and blood pressure modulation, which directly functions on lung, renal, brain, and vascular bed ion transport (13). Five DA receptors have been reported, indlucing DR1, DR2, DR3, DR4 an DR5 (14,15).…”

Section: Introductionmentioning

confidence: 99%

Fisetin inhibits liver cancer growth in a mouse model: Relation to dopamine receptor

et al. 2017

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Fisetin (3,3′,4′,7-tetrahydroxyflavone), a natural abundant flavonoid, is produced in different vegetables and fruits. Fisetin has been reported to relate to various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Dopamine receptors (DRs) belonging to G protein-coupled receptor family, are known as the target of ~50% of all modern medicinal drugs. DRs consist of various proteins, functioning as transduction of intracellular signals for extracellular stimuli. We found that fisetin performed as DR2 agonist to suppress liver cancer cells proliferation, migration and invasion. Caspase-3 signaling was activated to induce apoptosis for fisetin administration. Furthermore, TGF-β1 was also inhibited in fisetin-treated liver cancer cells, reducing epithelial-mesenchymal transition (EMT). Additionally, fisetin downregulated VEGFR1, p-ERK1/2, p38 and pJNK, ameliorating liver cancer progression. In vivo, the orthotopically implanted tumors from mice were inhibited by fisetin adminisatration accompanied by prolonged survival rate and higher levels of dopamine. Together, the results indicated a novel therapeutic strategy to suppress liver cancer progression associated with DR2 regulation, indicating that dopamine might be of importance in liver cancer progression.

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Dopamine, hypertension and obesity

Cited by 45 publications

References 47 publications

Reduction of renal dopamine receptor expression in obese Zucker rats: role of sex and angiotensin II

Reduction of renal dopamine receptor expression in obese Zucker rats: role of sex and angiotensin II

Transcriptional Regulation of Renal Dopamine D1 Receptor Function During Oxidative Stress

Fisetin inhibits liver cancer growth in a mouse model: Relation to dopamine receptor

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