ArticleHypertension research : official journal of the Japanese Society of Hypertension2015
Activation of the D4 dopamine receptor attenuates proliferation and migration of vascular smooth muscle cells through downregulation of AT1a receptor expression.
Article in Hypertension research : official journal of the Japanese Society of Hypertension, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 17 citations in OpenAlex.
- Pharmacological and immunohistochemical characterization of dopamine D4 receptor in human umbilical artery and vein.Vascular biology (Bristol, England) · 2025Article
- Effect of DCardiology discovery · 2023Article
- The Role of the Renal Dopaminergic System and Oxidative Stress in the Pathogenesis of Hypertension.Biomedicines · 2021Review
- Vasoplegia after implantation of a continuous flow left ventricular assist device: incidence, outcomes and predictors.BMC anesthesiology · 2018Article
- Activation of angiotensin II type 1 receptors increases DHypertension research : official journal of the Japanese Society of Hypertension · 2017Article
- Vascular structural and functional changes: their association with causality in hypertension: models, remodeling and relevance.Hypertension research : official journal of the Japanese Society of Hypertension · 2017Review
- Influence of periostin-positive cell-specific Klf5 deletion on aortic thickening in DOCA-salt hypertensive mice.Hypertension research : official journal of the Japanese Society of Hypertension · 2016Article
- Histone deacetyltransferase inhibitors Trichostatin A and Mocetinostat differentially regulate MMP9, IL-18 and RECK expression, and attenuate Angiotensin II-induced cardiac fibroblast migration and proliferation.Hypertension research : official journal of the Japanese Society of Hypertension · 2016Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Angiotensin (Ang) II has an important role in the vascular smooth muscle cell (VSMC) proliferation and migration and subsequently in the development of vascular diseases, whereas dopamine has the opposite effect. Previous studies have shown an interaction between dopamine and AT(1) receptors in the kidney. The dopamine D(4) receptor is expressed in arteries and has an inhibitory effect on VSMC proliferation. We hypothesized that the D(4) receptor, through its interaction with the AT(1a) receptor, may have an inhibitory effect on Ang II-mediated VSMC proliferation and migration, which could have a pivotal role in hypertension-induced vascular remodeling. In the current study, we found that Ang II markedly induced the proliferation and migration of A10 cells, which was inhibited by the D(4) receptor agonist PD168077. The activation of the D(4) receptor by PD168077 inhibited AT(1a) receptor expression in a concentration- and time-dependent manner. These effects were attenuated by silencing the D(4) receptor with a D(4) receptor-targeting small interfering RNA. The D(4) receptor-mediated inhibition of AT(1) receptor function involved protein kinase A (PKA). The activation of the D(4) receptor by PD168077 increased PKA activity in A10 cells, and the presence of a PKA inhibitor (PKA inhibitor 14-22, 10(-7) mol l(-1) per 24 h) blocked the inhibitory effect of the D(4) receptor on AT(1) receptor expression and function. The inhibitory effect of the D(4) receptor on AT(1) receptor expression and function was preserved in VSMCs (primary culture) from spontaneously hypertensive rats relative to VSMCs from Wistar-Kyoto rats. In conclusion, our data provide insight into the regulatory role of the D(4) receptor on AT(1a) receptor expression and function in VSMCs and suggest that targeting the action of the D(4) receptor may represent an effective therapeutic approach for the treatment of cardiovascular diseases.
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