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Dopamine receptors and hypertension

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Abstract

Dopamine plays an important role in regulating renal function and blood pressure. Dopamine synthesis and dopamine receptor subtypes have been shown in the kidney. Dopamine acts via cell surface receptors coupled to G proteins; the receptors are classified via pharmacologic and molecular cloning studies into two families, D1-like and D2-like. Two D1-like receptors cloned in mammals, the D1 and D5 receptors (D1A and D1B in rodents), are linked to adenylyl cyclase stimulation. Three D2-like receptors (D2, D3, and D4) have been cloned and are linked mainly to adenylyl cyclase inhibition. Activation of D1-like receptors on the proximal tubules inhibits tubular sodium reabsorption by inhibiting Na/H-exchanger and Na/K-adenosine triphosphatase activity. Reports exist of defective renal dopamine production and/or dopamine receptor function in human primary hypertension and in genetic models of animal hypertension. In humans with essential hypertension, renal dopamine production in response to sodium loading is often impaired and may contribute to hypertension. A primary defect in D1-like receptors and an altered signaling system in proximal tubules may reduce dopamine-mediated effects on renal sodium excretion. The molecular basis for dopamine receptor dysfunction in hypertension is being investigated, and may involve an abnormal posttranslational modification of the dopamine receptor.

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References and Recommended Reading

  1. Jose PA, Raymond JR, Bates MD, et al.: The renal dopamine receptors. J Am Soc Nephrol 1992, 2:1265–1278.

    PubMed  CAS  Google Scholar 

  2. Yoshimura M, Ikegaki I, Nishimura M, Takahashi H: Role of dopaminergic mechanisms in the kidney for the pathogenesis of hypertension. J Auton Pharmacol 1990, 10(Suppl 1):S67–S72.

    Article  PubMed  CAS  Google Scholar 

  3. Hussain T, Lokhandwala MF: Renal dopamine DA1 receptor coupling with G(S) and G(q/11) proteins in spontaneously hypertensive rats. Am J Physiol 1997, 272:F339–F346.

    PubMed  CAS  Google Scholar 

  4. Albrecht FE, Drago J, Felder RA, et al.: Role of the D1A dopamine receptor in the pathogenesis of genetic hypertension. J Clin Invest 1996, 97:2283–2288.

    Article  PubMed  CAS  Google Scholar 

  5. Zeng C, Armando I, Luo Y, et al.: Dysregulation of dopamine-dependent mechanisms as a determinant of hypertension: studies in dopamine receptor knockout mice. Am J Physiol Heart Circ Physiol 2008, 294:H551–H569.

    Article  PubMed  CAS  Google Scholar 

  6. Missale C, Nash SR, Robinson SW, et al.: Dopamine receptors: from structure to function. Physiol Rev 1998, 78:189–225.

    PubMed  CAS  Google Scholar 

  7. Lokhandwala MF, Amenta F: Anatomical distribution and function of dopamine receptors in the kidney. Faseb J 1991, 5:3023–3030.

    PubMed  CAS  Google Scholar 

  8. Goldberg LI: Cardiovascular and renal actions of dopamine: potential clinical applications. Pharmacol Rev 1972, 24:1–29.

    PubMed  CAS  Google Scholar 

  9. Frederickson ED, Bradley T, Goldberg LI: Blockade of renal effects of dopamine in the dog by the DA1 antagonist SCH 23390. Am J Physiol 1985, 249:F236–F240.

    PubMed  CAS  Google Scholar 

  10. Hahn RA, Wardell JR Jr: Renal vascular activity of SK&F 38393 and dopamine in anesthetized dogs. J Cardiovasc Pharmacol 2:583–593, 1980.

    Article  PubMed  CAS  Google Scholar 

  11. Hussain T, Lokhandwala MF: Renal dopamine receptors and hypertension. Exp Biol Med (Maywood) 228:134–142, 2003.

    CAS  Google Scholar 

  12. Hedge SS, Ricci A, Amenta F, Lokhandwala MF: Evidence from functional and autoradiographic studies for the presence of tubular dopamine-1 receptors and their involvement in the renal effects of fenoldopam. J Pharmacol Exp Ther 1989, 251:1237–1245.

    PubMed  CAS  Google Scholar 

  13. Romero-Vecchione E, Vasquez J, Lema G, et al.: Low urinary dopamine excretion associated to low sodium excretion in normotensive Piaroa Amazonian ethnia compared to urban subjects. Invest Clin 1995, 36:61–71.

    PubMed  CAS  Google Scholar 

  14. Chen CJ, Lokhandwala MF: Role of endogenous dopamine in the natriuretic response to various degrees of iso-osmotic volume expansion in rats. Clin Exp Hypertens A 1991, 13:1117–1126.

    Article  PubMed  CAS  Google Scholar 

  15. Hegde SS, Jadhav AL, Lokhandwala MF: Role of kidney dopamine in the natriuretic response to volume expansion in rats. Hypertension 1989, 13:828–834.

    PubMed  CAS  Google Scholar 

  16. Jose PA, Eisner GM, Felder RA: Renal dopamine and sodium homeostasis. Curr Hypertens Rep 2000, 2:174–183.

    Article  PubMed  CAS  Google Scholar 

  17. Bello-Reuss E, Higashi Y, Kaneda Y: Dopamine decreases fluid reabsorption in straight portions of rabbit proximal tubule. Am J Physiol 1982, 242:F634–F640.

    PubMed  CAS  Google Scholar 

  18. Aperia A, Bertorello A, Seri I: Dopamine causes inhibition of Na+-K+-ATPase activity in rat proximal convoluted tubule segments. Am J Physiol 1987, 252:F39–F45.

    PubMed  CAS  Google Scholar 

  19. Zeng C, Zhang M, Asico LD, et al.: The dopaminergic system in hypertension. Clin Sci (Lond) 2007, 112:583–597.

    Article  CAS  Google Scholar 

  20. Felder CC, Albrecht FE, Campbell T, et al.: cAMP-independent, G protein-linked inhibition of Na+/H+ exchange in renal brush border by D1 dopamine agonists. Am J Physiol 1993, 264:F1032–F1037.

    PubMed  CAS  Google Scholar 

  21. Felder CC, Campbell T, Albrecht F, Jose PA: Dopamine inhibits Na(+)-H+ exchanger activity in renal BBMV by stimulation of adenylate cyclase. Am J Physiol 1990, 259:F297–F303.

    PubMed  CAS  Google Scholar 

  22. Aperia AC: Intrarenal dopamine: a key signal in the interactive regulation of sodium metabolism. Annu Rev Physiol 2000, 62:621–647.

    Article  PubMed  CAS  Google Scholar 

  23. Horiuchi A, Takeyasu K, Mouradian MM, et al.: D1A dopamine receptor stimulation inhibits Na+/K(+)-ATPase activity through protein kinase A. Mol Pharmacol 1993, 43:281–285.

    PubMed  CAS  Google Scholar 

  24. Borin ML: Dual inhibitory effects of dopamine on Na+ homeostasis in rat aorta smooth muscle cells. Am J Physiol 1997, 272:C428–C438.

    PubMed  CAS  Google Scholar 

  25. Slobodyansky E, Aoki Y, Gaznabi AK, et al.: Dopamine and protein phosphatase activity in renal proximal tubules. Am J Physiol 1995, 268:F279–F284.

    PubMed  CAS  Google Scholar 

  26. Felder CC, McKelvey AM, Gitler MS, et al.: Dopamine receptor subtypes in renal brush border and basolateral membranes. Kidney Int 1989, 36:183–193.

    Article  PubMed  CAS  Google Scholar 

  27. Bertorello AM, Aperia A, Walaas SI, et al.: Phosphorylation of the catalytic subunit of Na+,K(+)-ATPase inhibits the activity of the enzyme. Proc Natl Acad Sci U S A 1991, 88:11359–11362.

    Article  PubMed  CAS  Google Scholar 

  28. Pedemonte CH, Pressley TA, Cinelli AR, Lokhandwala MF: Stimulation of protein kinase C rapidly reduces intracellular Na+ concentration via activation of the Na+ pump in OK cells. Mol Pharmacol 1997, 52:88–97.

    PubMed  CAS  Google Scholar 

  29. Beron J, Forster I, Beguin P, et al.: Phorbol 12-myristate 13-acetate down-regulates Na,K-ATPase independent of its protein kinase C site: decrease in basolateral cell surface area. Mol Biol Cell 1997, 8:387–398.

    PubMed  CAS  Google Scholar 

  30. Hussain T, Lokhandwala MF: Altered arachidonic acid metabolism contributes to the failure of dopamine to inhibit Na+,K(+)-ATPase in kidney of spontaneously hypertensive rats. Clin Exp Hypertens 1996, 18:963–974.

    Article  PubMed  CAS  Google Scholar 

  31. Chen C, Beach RE, Lokhandwala MF: Dopamine fails to inhibit renal tubular sodium pump in hypertensive rats. Hypertension 1993, 21:364–372.

    PubMed  CAS  Google Scholar 

  32. Kansra V, Chen C, Lokhandwala MF: Dopamine causes stimulation of protein kinase C in rat renal proximal tubules by activating dopamine D1 receptors. Eur J Pharmacol 1995, 289:391–394.

    Article  PubMed  CAS  Google Scholar 

  33. Yen TT, Yu PL, Roeder H, Willard PW: A genetic study of hypertension in Okamoto-Aoki spontaneously hypertensive rats. Heredity 1974, 33:309–316.

    Article  PubMed  CAS  Google Scholar 

  34. Andrejak M, Hary L: Enhanced dopamine renal responsiveness in patients with hypertension. Clin Pharmacol Ther 1986, 40:610–614.

    PubMed  CAS  Google Scholar 

  35. O’Connell DP, Ragsdale NV, Boyd DG, et al.: Differential human renal tubular responses to dopamine type 1 receptor stimulation are determined by blood pressure status. Hypertension 1997, 29:115–122.

    PubMed  CAS  Google Scholar 

  36. Iimura O, Shimamoto K: Suppressed dopaminergic activity and water-sodium handling in the kidneys at the prehypertensive stage of essential hypertension. J Auton Pharmacol 1990, 10(Suppl 1):S73–S77.

    PubMed  CAS  Google Scholar 

  37. Jose PA, Eisner GM, Drago J, et al.: Dopamine receptor signaling defects in spontaneous hypertension. Am J Hypertens 1996, 9:400–405.

    Article  PubMed  CAS  Google Scholar 

  38. Zeng C, Sanada H, Watanabe H, et al.: Functional genomics of the dopaminergic system in hypertension. Physiol Genomics 2004, 19:233–246.

    Article  PubMed  CAS  Google Scholar 

  39. Nishi A, Eklof AC, Bertorello AM, Aperia A: Dopamine regulation of renal Na+,K(+)-ATPase activity is lacking in Dahl salt-sensitive rats. Hypertension 1993, 21:767–771.

    PubMed  CAS  Google Scholar 

  40. Ohbu K, Kaskel FJ, Kinoshita S, Felder RA: Dopamine-1 receptors in the proximal convoluted tubule of Dahl rats: defective coupling to adenylate cyclase. Am J Physiol 1995, 268:R231–R235.

    PubMed  CAS  Google Scholar 

  41. Kinoshita S, Sidhu A, Felder RA: Defective dopamine-1 receptor adenylate cyclase coupling in the proximal convoluted tubule from the spontaneously hypertensive rat. J Clin Invest 1989, 84:1849–1856.

    Article  PubMed  CAS  Google Scholar 

  42. Horiuchi A, Albrecht FE, Eisner GM, et al.: Renal dopamine receptors and pre-and post-cAMP-mediated Na+ transport defect in spontaneously hypertensive rats. Am J Physiol 1992, 263:F1105–F1111.

    PubMed  CAS  Google Scholar 

  43. Paravicini TM, Touyz RM: Redox signaling in hypertension. Cardiovasc Res 2006, 71:247–258.

    Article  PubMed  CAS  Google Scholar 

  44. Landmesser U, Cai H, Dikalov S, et al.: Role of p47(phox) in vascular oxidative stress and hypertension caused by angiotensin II. Hypertension 2002, 40:511–515.

    Article  PubMed  CAS  Google Scholar 

  45. Redon J, Oliva MR, Tormos C, et al.: Antioxidant activities and oxidative stress byproducts in human hypertension. Hypertension 2003, 41:1096–1101.

    Article  PubMed  CAS  Google Scholar 

  46. Banday AA, Fazili FR, Lokhandwala MF: Oxidative stress causes renal dopamine D1 receptor dysfunction and hypertension via mechanisms that involve nuclear factor-kappaB and protein kinase C. J Am Soc Nephrol 2007, 18:1446–1457.

    Article  PubMed  CAS  Google Scholar 

  47. Banday AA, Lau YS, Lokhandwala MF: Oxidative stress causes renal dopamine D1 receptor dysfunction and salt-sensitive hypertension in Sprague-Dawley rats. Hypertension 2008, 51:367–375.

    Article  PubMed  CAS  Google Scholar 

  48. Banday AA, Marwaha A, Tallam LS, Lokhandwala MF: Tempol reduces oxidative stress, improves insulin sensitivity, decreases renal dopamine D1 receptor hyperphosphorylation, and restores D1 receptor-G-protein coupling and function in obese Zucker rats. Diabetes 2005, 54:2219–2226.

    Article  PubMed  CAS  Google Scholar 

  49. Yang Z, Asico LD, Yu P, et al.: D5 dopamine receptor regulation of phospholipase D. Am J Physiol Heart Circ Physiol 2005, 288:H55–H61.

    Article  PubMed  CAS  Google Scholar 

  50. Yang Z, Asico LD, Yu P, et al.: D5 dopamine receptor regulation of reactive oxygen species production, NADPH oxidase, and blood pressure. Am J Physiol Regul Integr Comp Physiol 2006, 290:R96–R104.

    PubMed  CAS  Google Scholar 

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Correspondence to Anees Ahmad Banday.

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Banday, A.A., Lokhandwala, M.F. Dopamine receptors and hypertension. Current Science Inc 10, 268–275 (2008). https://doi.org/10.1007/s11906-008-0051-9

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