This Article Full Text Full Text (PDF) All Versions of this Article: 40/6/880    most recent 01.HYP.0000039963.01288.D3v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Umrani, D. N. Articles by Lokhandwala, M. F. Search for Related Content PubMed PubMed Citation Articles by Umrani, D. N. Articles by Lokhandwala, M. F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB DOPAMINE GLUCOSE Medline Plus Health Information Obesity Related Collections Obesity Hypertension - basic studies Type 2 diabetes

(Hypertension. 2002;40:880.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Rosiglitazone Treatment Restores Renal Dopamine Receptor Function in Obese Zucker Rats

From the Heart and Kidney Institute, College of Pharmacy, University of Houston, Houston, Tex.

Correspondence to Dr Mustafa F. Lokhandwala, College of Pharmacy, University of Houston, Houston, TX 77204. E-mail MLokhandwala{at}uh.edu

Earlier we have reported a defective dopamine D₁–like receptor function, which was accompanied by a decrease in D1 receptor numbers and the inability of dopamine to inhibit Na,K-ATPase and Na,H-exchanger in proximal tubules of hyperinsulinemic obese Zucker rats. The present study was designed to test the hypothesis that the defect in dopamine receptor function is a result of hyperinsulinemia in obese rats. We designed experiments to study D1 receptor function in obese Zucker rats treated with rosiglitazone, as it lowers plasma insulin by improving insulin sensitivity. A group of untreated lean and obese rats served as controls. Rosiglitazone treatment (10 mg/kg orally, 4 weeks) caused significant decreases in plasma insulin, blood glucose, and blood pressure while causing an increase in renal sodium excretion compared with untreated obese rats. In the isolated proximal tubules obtained from untreated lean rats, dopamine caused concentration-dependent inhibition of the Na,K-ATPase activity, but this inhibitory effect was absent in untreated obese rats. In rosiglitazone-treated obese rats, the inhibitory effect of dopamine on Na,K-ATPase was significantly restored. This was accompanied by a complete restoration of D1 receptor numbers in proximal tubular membranes of treated obese rats. In another set of experiments, treatment of primary proximal tubule epithelial cells in culture medium with insulin caused a significant decrease in the D1 receptor abundance, suggesting a direct role of insulin on D1 receptor regulation. We conclude that hyperinsulinemia causes downregulation of D1 receptor function and lowering of plasma insulin levels leads to restoration of renal D1 receptor function.

Key Words: receptors, dopamine • hyperinsulinism • obesity • rats, Zucker

This article has been cited by other articles:

				S. Tiwari, S. Riazi, and C. A. Ecelbarger Insulin's impact on renal sodium transport and blood pressure in health, obesity, and diabetes Am J Physiol Renal Physiol, October 1, 2007; 293(4): F974 - F984. [Abstract] [Full Text] [PDF]

				A. A. Banday, F. R. Fazili, and M. F. Lokhandwala Oxidative Stress Causes Renal Dopamine D1 Receptor Dysfunction and Hypertension via Mechanisms That Involve Nuclear Factor-{kappa}B and Protein Kinase C J. Am. Soc. Nephrol., May 1, 2007; 18(5): 1446 - 1457. [Abstract] [Full Text] [PDF]

				A. Zanchi, C. Perregaux, M. Maillard, D. Cefai, J. Nussberger, and M. Burnier The PPAR{gamma} agonist pioglitazone modifies the vascular sodium-angiotensin II relationship in insulin-resistant rats Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1228 - E1234. [Abstract] [Full Text] [PDF]

				M. Trivedi and M. F. Lokhandwala Rosiglitazone restores renal D1A receptor-Gs protein coupling by reducing receptor hyperphosphorylation in obese rats Am J Physiol Renal Physiol, August 1, 2005; 289(2): F298 - F304. [Abstract] [Full Text] [PDF]

				O. Khan, S. Riazi, X. Hu, J. Song, J. B. Wade, and C. A. Ecelbarger Regulation of the renal thiazide-sensitive Na-Cl cotransporter, blood pressure, and natriuresis in obese Zucker rats treated with rosiglitazone Am J Physiol Renal Physiol, August 1, 2005; 289(2): F442 - F450. [Abstract] [Full Text] [PDF]

				A. A. Banday, T. Hussain, and M. F. Lokhandwala Renal dopamine D1 receptor dysfunction is acquired and not inherited in obese Zucker rats Am J Physiol Renal Physiol, July 1, 2004; 287(1): F109 - F116. [Abstract] [Full Text] [PDF]

				A. Marwaha, A. A. Banday, and M. F. Lokhandwala Reduced renal dopamine D1 receptor function in streptozotocin-induced diabetic rats Am J Physiol Renal Physiol, March 1, 2004; 286(3): F451 - F457. [Abstract] [Full Text]

				M. Trivedi, A. Marwaha, and M. Lokhandwala Rosiglitazone Restores G-Protein Coupling, Recruitment, and Function of Renal Dopamine D1A Receptor in Obese Zucker Rats Hypertension, February 1, 2004; 43(2): 376 - 382. [Abstract] [Full Text] [PDF]

				C. V. Desouza, S. N. Murthy, J. Diez, B. Dunne, A. S. Matta, V. A. Fonseca, and D. B. McNamara Differential Effects of Peroxisome Proliferator Activator Receptor-{alpha} and {gamma} Ligands on Intimal Hyperplasia After Balloon Catheter-Induced Vascular Injury in Zucker Rats Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2003; 8(4): 297 - 305. [Abstract] [PDF]

				A. A. Banday, M. Asghar, T. Hussain, and M. F. Lokhandwala Dopamine-Mediated Inhibition of Renal Na,K-ATPase Is Reduced by Insulin Hypertension, June 1, 2003; 41(6): 1353 - 1358. [Abstract] [Full Text] [PDF]