Dopamine-Mediated Inhibition of Renal Na,K-ATPase Is Reduced by Insulin

Banday, Anees Ahmad; Asghar, Mohammad; Hussain, Tahir; Lokhandwala, Mustafa F.

doi:10.1161/01.hyp.0000069260.11830.cd

Cited by 28 publications

(31 citation statements)

References 52 publications

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“…However, endogenous renal dopamine production is normal or even increased in obese humans (46), monkeys (43), and rats (39). Therefore, the dopaminergic defect in the obese male rat has been suggested to be at the receptor or postreceptor level (4,5,7,23,24,40). Our finding of decreased renal expression of D1R in obese male rats provides a potential explanation for the reduced D1-like dopaminergic signaling previously reported in the proximal tubule of these rats (5,31).…”

Section: Discussionmentioning

confidence: 50%

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: 50%

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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“…In proximal tubular cell culture insulin is shown to down regulate the dopamine D 1 receptors and cause uncoupling of D 1 receptors from G proteins (9). Several groups have suggested that hyperinsulinemia may lead to an increase in sodium reabsorption (10,11).…”

Section: Discussionmentioning

confidence: 99%

Diminished Natriuretic Response to Dopamine D₁Receptor Agonist, SKF‐38393 in Obese Zucker Rats

Marwaha

Lokhandwala

2003

Clinical and Experimental Hypertension

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Dopamine causes natriuresis and diuresis via activation of D1 receptors located on the renal proximal tubules and subsequent inhibition of the sodium transporters, Na-H exchanger and Na+/K+ ATPase. We have reported that dopamine fails to inhibit the activities of these two transporters in the obese Zucker rats (OZR). The present study was designed to examine the functional consequence of this phenomenon by determining the natriuretic and diuretic response to D1 receptor activation in lean Zucker rats (LZR) and OZR. In 11-12 week-old OZR and LZR, natriuretic and diuretic responses to intravenously administered D1 receptor agonist, SKF 38393 (3 microg/kg/min for 30 min) were measured under Inactin anesthesia. Plasma insulin and glucose levels were significantly higher in the obese rats as compared to the lean rats. Intravenous infusion of SKF 38393 caused significant increases in urine flow, urinary sodium excretion (U(Na)V), fractional excretion of sodium (FE(Na)), and glomerular filtration rate (GFR) in the lean rats. However, the natriuretic and diuretic response to SKF 38393 was markedly blunted in OZR. Infusion of SKF 38393 did not cause significant changes in the mean blood pressure and heart rate in either of the two groups. We suggest that the diminished natriuretic response to D1 receptor activation in OZR is the consequence of the previously reported defect in the D1 receptor-G-protein coupling and the failure of dopamine to inhibit the sodium transporters in these animals.

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“…Primary cell cultures grown in 12-well plates were used for 86 Rb uptake measurement according to our published method (5). The cells were incubated without or with SKF-38393 for 10 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Renal proximal tubules from old Fischer 344 rats grow into epithelial cells in cultures and exhibit increased oxidative stress and reduced D1 receptor function

Asghar¹,

Chillar²,

Lokhandwala³

2008

American Journal of Physiology-Cell Physiology

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Asghar M, Chillar A, Lokhandwala MF. Renal proximal tubules from old Fischer 344 rats grow into epithelial cells in cultures and exhibit increased oxidative stress and reduced D1 receptor function. Am J Physiol Cell Physiol 295: C1326 -C1331, 2008. First published September 17, 2008 doi:10.1152/ajpcell.00367.2008.-Earlier we reported defects in D1 receptor function in renal proximal tubules (RPTs) of aged Fischer 344 (F344) and obese Zucker rats. However, the defects in the receptor function in RPTs of obese Zucker rats do not pass onto primary cultures of RPTs from these animals. Here, we determined whether the defects in D1 receptor function in RPTs of aged F344 rats pass onto the primary cultures. RPTs from aged (24-mo) and adult (6-mo) F344 rats were grown into primary cultures. The microscopic studies showed that cells in cultures from adult and old rats were healthy as determined by the shape and size of the cells and nuclei. D1 receptor agonist SKF-38393 produced inhibition of 86 Rb (rubidium) uptake, index of Na-K-ATPase activity, in cells from adult rats, but this was reduced in old rats. Also, SKF-38393 increased the [35 S]GTP␥S binding, index of receptor activation, in the membranes of cells from adult rats but to a lesser extent from old rats. Furthermore, there was a downward trend in the levels of D1 receptor numbers and in the receptor proteins in old rats. Interestingly, gp 91phox subunit of NADPH oxidase and cellular protein carbonyl levels (oxidative stress marker) were higher in cultures from old rats. These results show that RPTs from adult and old F344 rats grow into epithelial cells in cultures. Furthermore, cells in cultures from old rats are at a higher level of oxidative stress, which may be contributing to the reduced D1 receptor function in the cells from old compared with adult rats. dopamine; NADPH oxidase; G protein-coupled receptor; aging DURING INCREASED SODIUM INTAKE renal dopamine maintains sodium homeostasis by promoting sodium excretion via activation of D1 receptor and inhibition of sodium transporter Na-K-ATPase in renal proximal tubules (RPT) (1,9,19,20). Diminished D1 receptor signaling in RPT has been linked to the reduced natriuretic response to dopamine and development of hypertension in animals and humans (16,25,34).Aging initiates various structural and functional changes in several body organs including in the kidney (13). In the elderly, reduced ability of the kidney to respond to dopamine and increase sodium excretion during salt loading has been linked to the development of age-associated hypertension (33). In old Fischer 344 rats (F344), renal dopamine D1 receptor function is also impaired, partly due to reduced D1 receptor G protein coupling in RPT, resulting in diminished natriuretic response to dopamine in aging (6). Age-related increase in oxidative stress has been linked to uncoupling of D1 receptors from G proteins leading to D1 receptor dysfunction in RPTs of old rats (14).Primary cell cultures from different organs such as the brain, heart, and kidney ha...

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Dopamine-Mediated Inhibition of Renal Na,K-ATPase Is Reduced by Insulin

Cited by 28 publications

References 52 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

Diminished Natriuretic Response to Dopamine D₁Receptor Agonist, SKF‐38393 in Obese Zucker Rats

Renal proximal tubules from old Fischer 344 rats grow into epithelial cells in cultures and exhibit increased oxidative stress and reduced D1 receptor function

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Dopamine-Mediated Inhibition of Renal Na,K-ATPase Is Reduced by Insulin

Cited by 28 publications

References 52 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

Diminished Natriuretic Response to Dopamine D1Receptor Agonist, SKF‐38393 in Obese Zucker Rats

Renal proximal tubules from old Fischer 344 rats grow into epithelial cells in cultures and exhibit increased oxidative stress and reduced D1 receptor function

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Diminished Natriuretic Response to Dopamine D₁Receptor Agonist, SKF‐38393 in Obese Zucker Rats