scholarly journals Rosiglitazone Treatment Restores Renal Dopamine Receptor Function in Obese Zucker Rats

Hypertension ◽  
2002 ◽  
Vol 40 (6) ◽  
pp. 880-885 ◽  
Author(s):  
Dhananjay N. Umrani ◽  
Anees A. Banday ◽  
Tahir Hussain ◽  
Mustafa F. Lokhandwala
Keyword(s):  
Dopamine Receptor ◽  
Zucker Rats ◽  
Receptor Function ◽  
Obese Zucker Rats ◽  
Rosiglitazone Treatment ◽  
Renal Dopamine

Renal dopamine D1 receptor dysfunction is acquired and not inherited in obese Zucker rats

2004 ◽  
Vol 287 (1) ◽  
pp. F109-F116 ◽  
Author(s):  
Anees Ahmad Banday ◽  
Tahir Hussain ◽  
Mustafa F. Lokhandwala
Keyword(s):  
G Protein ◽  
D1 Receptor ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Zucker Rats ◽  
Receptor Function ◽  
Rat Serum ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Renal Dopamine

In essential hypertension, the defect in renal dopamine (DA) D1 receptor function is intrinsic to proximal tubules as this phenomenon is also seen in primary proximal tubule cultures from spontaneously hypertensive rats (SHR) and essential hypertensive patients. Previously, a defect was reported in renal D1 receptor function in obese Zucker rats. In the present study, we sought to determine whether this D1 receptor dysfunction is intrinsic in these animals. In primary proximal tubular epithelial cells (PTECs) from lean and obese rats, DA inhibited Na-K-ATPase (NKA) activity in PTECs from both groups of rats. Basal NKA activity, D1 receptor protein expression, and their coupling to G proteins were similar in cells from both groups. However, when PTECs from lean and obese rats were cultured in 20% serum from obese rats, DA failed to inhibit NKA activity, which was accompanied by a reduction in D1 receptor expression and a defect in D1 receptor-G protein coupling. No such defects in the inhibitory effect of DA on NKA activity, D1 receptor numbers, or coupling were seen when PTECs from both lean and obese rats were grown in 20% serum from lean or rosiglitazone-treated obese (RTO) rats. RTO rat serum had normal blood glucose and reduced plasma levels of insulin compared with serum from obese rats. Furthermore, chronic insulin treatment of PTECs from lean and obese rats caused an attenuation in DA-induced NKA inhibition, a decrease in D1 receptor expression, and D1 receptor-G protein uncoupling. These results suggest that defective D1 receptor function in obese Zucker rats is not inherited but contributed to by hyperinsulinemia and/or other circulating factors associated with obesity.

scholarly journals Defective Dopamine Receptor Function in Proximal Tubules of Obese Zucker Rats

Hypertension ◽  
1999 ◽  
Vol 34 (5) ◽  
pp. 1091-1096 ◽  
Author(s):  
Tahir Hussain ◽  
Sucheta A. Beheray ◽  
Mustafa F. Lokhandwala
Keyword(s):  
Dopamine Receptor ◽  
Proximal Tubules ◽  
Zucker Rats ◽  
Receptor Function ◽  
Obese Zucker Rats

scholarly journals Rosiglitazone Enhances Glucose Tolerance by Mechanisms Other than Reduction of Fatty Acid Accumulation within Skeletal Muscle

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5665-5670 ◽  
Author(s):  
Sarah J. Lessard ◽  
Sonia L. Lo Giudice ◽  
Winnie Lau ◽  
Julianne J. Reid ◽  
Nigel Turner ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Glucose Tolerance ◽  
Dry Mass ◽  
Zucker Rats ◽  
Control Group ◽  
Fatty Acid Accumulation ◽  
Acid Accumulation ◽  
Obese Zucker Rats ◽  
Rosiglitazone Treatment

Abstract We hypothesized that improved glucose tolerance with rosiglitazone treatment would coincide with decreased levels of im triacylglycerol (IMTG), diacylglycerol, and ceramide. Obese Zucker rats were randomly divided into two experimental groups: control (n = 9) and rosiglitazone (n = 9), with lean Zucker rats (n = 9) acting as a control group for obese controls. Rats received either vehicle or 3 mg/kg rosiglitazone for 6 wk. Glucose tolerance was impaired (P < 0.01) in obese compared with lean rats, but was normalized after rosiglitazone treatment. IMTG content was higher in obese compared with lean rats (70.5 ± 5.1 vs. 27.5 ± 2.0 μmol/g dry mass; P < 0.05) and increased an additional 30% (P < 0.05) with rosiglitazone treatment. Intramuscular fatty acid composition shifted toward a higher proportion of monounsaturates (P < 0.05) in obese rosiglitazone-treated rats due to an increase in palmitoleate (16:1; P < 0.05). Rosiglitazone treatment increased (P < 0.05) skeletal muscle diacylglycerol and ceramide levels by 65% and 100%, respectively, compared with obese rats, but elevated muscle diacylglycerol was not associated with changes in the total or membrane contents of the diacylglycerol-sensitive protein kinase C isoforms θ, δ, α, and β. In summary, we observed a disassociation among skeletal muscle IMTG, diacylglycerol and ceramide content, and glucose tolerance with rosiglitazone treatment in obese Zucker rats. Our data suggest, therefore, that rosiglitazone enhances glucose tolerance by mechanisms other than reduction of fatty acid accumulation within skeletal muscle.

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

2008 ◽  
Vol 295 (5) ◽  
pp. C1326-C1331 ◽  
Author(s):  
Mohammad Asghar ◽  
Annirudha Chillar ◽  
Mustafa F. Lokhandwala
Keyword(s):  
Oxidative Stress ◽  
Primary Cultures ◽  
D1 Receptor ◽  
Zucker Rats ◽  
Receptor Function ◽  
Adult Rats ◽  
Fischer 344 ◽  
Old Rats ◽  
Obese Zucker Rats ◽  
F344 Rats

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 86Rb (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 [35S]GTPγS 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.

Renal Dopamine Receptors and Hypertension

2003 ◽  
Vol 228 (2) ◽  
pp. 134-142 ◽  
Author(s):  
Tahir Hussain ◽  
Mustafa F. Lokhandwala
Keyword(s):  
Proximal Tubule ◽  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
Sodium Excretion ◽  
Molecular Mechanisms ◽  
Sympathetic Ganglia ◽  
Receptor Subtypes ◽  
Receptor Function ◽  
The Central Nervous System ◽  
Renal Dopamine

Dopamine has been recognized as an important modulator of central as well as peripheral physiologic functions in both humans and animals. Dopamine receptors have been identified in a number of organs and tissues, which Include several regions within the central nervous system, sympathetic ganglia and postganglionic nerve terminals, various vascular beds, the heart, the gastrointestinal tract, and the kidney. The peripheral dopamine receptors influence cardiovascular and renal function by decreasing afterload and vascular resistance and promoting sodium excretion. Within the kidney, dopamine receptors are present along the nephron, with highest density on proximal tubule epithelial cells. It has been reported that there is a defective dopamine receptor, especially D1 receptor function, in the proximal tubule of various animal models of hypertension as well as in humans with essential hypertension. Recent reports have revealed the site of and the molecular mechanisms responsible for the defect in D1 receptors in hypertension. Moreover, recent studies have also demonstrated that the disruption of various dopamine receptor subtypes and their function produces hypertension in rodents. In this review, we present evidence that dopamine and dopamine receptors play an important role in regulating renal sodium excretion and that defective renal dopamine production and/or dopamine receptor function may contribute to the development of various forms of hypertension.

scholarly journals Renal Dopamine Receptor Function in Hypertension

Hypertension ◽  
1998 ◽  
Vol 32 (2) ◽  
pp. 187-197 ◽  
Author(s):  
Tahir Hussain ◽  
Mustafa F. Lokhandwala
Keyword(s):  
Dopamine Receptor ◽  
Receptor Function ◽  
Renal Dopamine
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