Arterial Blood Pressure and Renal Sodium Excretion in Dopamine D3 Receptor Knockout Mice

Staudacher, Torsten; Pech, Bärbel; Tappe, Michael; Groß, Gerhard; Mühlbauer, Bernd; Luippold, Gerd

doi:10.1291/hypres.30.93

Cited by 29 publications

(27 citation statements)

References 20 publications

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“…Maneuvers that chronically disrupt DA-dependent natriuresis such as blockade of DA generation by inhibitors of aromatic amino acid decarboxylase (14,95), pharmacological antagonism of dopamine receptors (51,55,70,84,94), and genetic deletion of DA receptors (DR 1 through DR 5 in isolation) all lead to systemic hypertension with a plethora of renal and extrarenal pathophysiological changes (1, 10,19,58,75,114,118,120). Some degree of impaired natriuresis has been described in several although not all of the single DA receptor gene deletion models (10,98). The spontaneously hypertensive and Dahl salt-sensitive rat models of polygenic hypertension exhibit lesions along the intrarenal dopamine-natriuresis axis including defective downstream effectors of DA action (48,62,99,115).…”

Section: Discussionmentioning

confidence: 99%

Chronic regulation of the renal Na⁺/H⁺exchanger NHE3 by dopamine: translational and posttranslational mechanisms

Sole

Zhang

et al. 2013

American Journal of Physiology-Renal Physiology

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The intrarenal autocrine/paracrine dopamine (DA) system contributes to natriuresis in response to both acute and chronic Na+ loads. While the acute DA effect is well described, how DA induces natriuresis chronically is not known. We used an animal and a cell culture model to study the chronic effect of DA on a principal renal Na+ transporter, Na+/H+ exchanger-3 (NHE3). Intraperitoneal injection of Gludopa in rats for 2 days elevated DA excretion and decreased total renal cortical and apical brush-border NHE3 antigen. Chronic treatment of an opossum renal proximal cell line with DA decreased NHE3 activity, cell surface and total cellular NHE3 antigen, but not NHE3 transcript. The decrease in NHE3 antigen was dose and time dependent with maximal inhibition at 16–24 h and half maximal effect at 3 × 10−7 M. This is in contradistinction to the acute effect of DA on NHE3 (half maximal at 2 × 10−6 M), which was not associated with changes in total cellular NHE3 protein. The DA-induced decrease in total NHE3 protein was associated with decrease in NHE3 translation and mediated by cis-sequences in the NHE3 5′-untranslated region. DA also decreased cell surface and total cellular NHE3 protein half-life. The DA-induced decrease in total cellular NHE3 was partially blocked by proteasome inhibition but not by lysosome inhibition, and DA increased ubiquitylation of total and surface NHE3. In summary, chronic DA inhibits NHE3 with mechanisms distinct from its acute action and involves decreased NHE3 translation and increased NHE3 degradation, which are novel mechanisms for NHE3 regulation.

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Section: Discussionmentioning

confidence: 99%

Chronic regulation of the renal Na⁺/H⁺exchanger NHE3 by dopamine: translational and posttranslational mechanisms

Sole

Zhang

et al. 2013

American Journal of Physiology-Renal Physiology

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“…Ten days prior and during the first 10 days of losartan treatment, blood pressure was measured by the tail cuff method using a blood pressure analyzer (Hugo Sachs, March-Hugstetten, Germany) as described elsewhere. 12 Germany) dissolved in in 24 mL of 0.9% NaCl was applied intranasally (10 mg=kg body weight) every other day for a period of 2 months. Thereafter, the mice were sacrificed under ketamine anesthesia (75 mg=kg, intraperitoneally [i.p.…”

Section: Methodsmentioning

confidence: 99%

Protective Effects of Intranasal Losartan in the APP/PS1 Transgenic Mouse Model of Alzheimer Disease

Danielyan

Klein

Hanson

et al. 2010

Rejuvenation Research

138

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The local renin-angiotensin system (RAS) in the brain is a multitasking system controlling a plethora of essential functions such as neurogenic hypertension, baroreflexes, and sympathetic activity. Aside from its vasoactive actions, brain angiotensin II (AT-II) has also been implicated in the pathogenesis of cognitive decline, and beneficial effects of angiotensin receptor blockers (ARBs) in Alzheimer (AD) and Parkinson diseases (PD) are suggested. However, the use of ARBs at antihypertensive dosages would lead to unwanted hypotensive reactions in AD patients. Here we treated the APP/PS1 transgenic mouse model of AD with the ARB losartan (10 mg/kg body weight) to determine whether blockade of the AT-II receptor subtype 1 (AT1-R) with intranasal losartan, using at a dosage far below its systemic antihypertensive dose, could maintain its neuroprotective effects independent of its systemic vasoactive action. Intranasal losartan treatment (10 mg/kg every other day for 2 months) of APP/PS1 mice decreased amyloid beta (Abeta) plaques 3.7-fold. Blood serum levels of interleukin-12 (IL-12)p40/p70, IL-1beta, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased in the vehicle-treated APP/PS1 mice. Intranasal losartan not only decreased IL-12p40/p70, IL-1beta, and GM-CSF, but also increased IL-10, which suppresses inflammation. Furthermore, losartan markedly increased tyrosine hydroxylase expression in the striatum and locus coeruleus. In conclusion, losartan exerts direct neuroprotective effects via its Abeta-reducing and antiinflammatory effects in the central nervous system (CNS). Therefore, intranasal losartan and potentially other ARBs, at concentrations below their threshold for altering systemic blood pressure, offer a new approach for the treatment of AD.

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“…Depending on the genetic background [59,[79][80][81], knockout of all the dopamine-receptor gene subtypes in mice causes hypertension that can be aggravated by an increase in sodium chloride intake in D2 −/− , D3 −/− , D4 −/− , and D5 −/− mice; salt sensitivity of D1 −/− mice has not been tested.…”

Section: Genetic Evidence For the Role Of The D1 Receptor In Hypertenmentioning

confidence: 99%

Potential Dopamine-1 Receptor Stimulation in Hypertension Management

et al. 2011

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The role of dopamine receptors in blood pressure regulation is well established. Genetic ablation of both dopamine D1-like receptor subtypes (D1, D5) and D2-like receptor subtypes (D2, D3, D4) results in a hypertensive phenotype in mice. This review focuses on the dopamine D1-like receptor subtypes D1 and D5 (especially D1 receptors), as they play a major role in regulating sodium homeostasis and blood pressure. Studies mostly describing the role of renal dopamine D1-like receptors are included, as the kidneys play a pivotal role in the maintenance of sodium homeostasis and the long-term regulation of blood pressure. We also attempt to describe the interaction between D1-like receptors and other proteins, especially angiotensin II type 1 and type 2 receptors, which are involved in the maintenance of sodium homeostasis and blood pressure. Finally, we discuss a new concept of renal D1 receptor regulation in hypertension that involves oxidative stress mechanisms.

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Arterial Blood Pressure and Renal Sodium Excretion in Dopamine D3 Receptor Knockout Mice

Cited by 29 publications

References 20 publications

Chronic regulation of the renal Na⁺/H⁺exchanger NHE3 by dopamine: translational and posttranslational mechanisms

Chronic regulation of the renal Na⁺/H⁺exchanger NHE3 by dopamine: translational and posttranslational mechanisms

Protective Effects of Intranasal Losartan in the APP/PS1 Transgenic Mouse Model of Alzheimer Disease

Potential Dopamine-1 Receptor Stimulation in Hypertension Management

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Arterial Blood Pressure and Renal Sodium Excretion in Dopamine D3 Receptor Knockout Mice

Cited by 29 publications

References 20 publications

Chronic regulation of the renal Na+/H+exchanger NHE3 by dopamine: translational and posttranslational mechanisms

Chronic regulation of the renal Na+/H+exchanger NHE3 by dopamine: translational and posttranslational mechanisms

Protective Effects of Intranasal Losartan in the APP/PS1 Transgenic Mouse Model of Alzheimer Disease

Potential Dopamine-1 Receptor Stimulation in Hypertension Management

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Chronic regulation of the renal Na⁺/H⁺exchanger NHE3 by dopamine: translational and posttranslational mechanisms

Chronic regulation of the renal Na⁺/H⁺exchanger NHE3 by dopamine: translational and posttranslational mechanisms