Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1990;30(Suppl 1):61S–68S. doi: 10.1111/j.1365-2125.1990.tb05470.x

The role of DA1- and DA2-receptors in the control of blood pressure

J P Hieble, R J Eden, C de Mey
PMCID: PMC1368100  PMID: 1980080

Abstract

1 Endogenous dopamine, acting through specific receptors on blood vessels, renal tubules and adrenal cortical cells, may play a role in the development and maintenance of the hypertensive state.

2 In hypertensive patients, activation of the DA1-receptor with intravenous fenoldopam produces a rapid and sustained reduction in blood pressure, in contrast to the tachyphylaxis seen in some rat models.

3 Activation of the DA2-receptor also represents a viable antihypertensive approach, based on the chronic efficacy of hydergine. However, none of the recently developed selective DA2-receptor agonists has been shown to reduce blood pressure in man.

4 Since animal experiments suggest qualitatively different antihypertensive profiles for quinpirole and SK&F 101468, both presumed to be selective agonists at the DA2-receptor, it may be possible to design new DA2-receptor agonists more effective as antihypertensive drugs.

5 Dopamine receptors at different sites, even if of the same subtype, can be differentially regulated; this may be a consequence of activation of multiple second messenger systems by receptor occupation.

Keywords: dopamine, blood pressure, DA1-receptor, DA2-receptor

Full text

PDF
61S

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bell C. Endogenous renal dopamine and control of blood pressure. Clin Exp Hypertens A. 1987;9(5-6):955–975. doi: 10.3109/10641968709161459. [DOI] [PubMed] [Google Scholar]
  2. Bell C., Lang W. J., Laska F. Dopamine-containing axons supplying the arterio-venous anastomoses of the canine paw pad. J Neurochem. 1978 Nov;31(5):1329–1333. doi: 10.1111/j.1471-4159.1978.tb06259.x. [DOI] [PubMed] [Google Scholar]
  3. Bunzow J. R., Van Tol H. H., Grandy D. K., Albert P., Salon J., Christie M., Machida C. A., Neve K. A., Civelli O. Cloning and expression of a rat D2 dopamine receptor cDNA. Nature. 1988 Dec 22;336(6201):783–787. doi: 10.1038/336783a0. [DOI] [PubMed] [Google Scholar]
  4. Clark B. J. Is stimulation of prejunctional dopamine receptors an antihypertensive principle? Clin Exp Hypertens A. 1987;9(5-6):1045–1068. doi: 10.3109/10641968709161465. [DOI] [PubMed] [Google Scholar]
  5. Felder C. C., Jose P. A., Axelrod J. The dopamine-1 agonist, SKF 82526, stimulates phospholipase-C activity independent of adenylate cyclase. J Pharmacol Exp Ther. 1989 Jan;248(1):171–175. [PubMed] [Google Scholar]
  6. Felder R. A., Blecher M., Calcagno P. L., Jose P. A. Dopamine receptors in the proximal tubule of the rabbit. Am J Physiol. 1984 Sep;247(3 Pt 2):F499–F505. doi: 10.1152/ajprenal.1984.247.3.F499. [DOI] [PubMed] [Google Scholar]
  7. Goldberg L. I., Murphy M. B. Potential use of DA1 and DA2 receptor agonists in the treatment of hypertension. Clin Exp Hypertens A. 1987;9(5-6):1023–1035. doi: 10.3109/10641968709161463. [DOI] [PubMed] [Google Scholar]
  8. Guffanti E., Vaccarella A., Meregalli M., Fiorella G., Chierichetti S. M., Mazzola C. A single blind comparison of dihydroergotoxine mesilate and clonidine for treatment of hypertensive emergencies. Int J Clin Pharmacol Ther Toxicol. 1985 Sep;23(9):506–509. [PubMed] [Google Scholar]
  9. Harvey J. N., Worth D. P., Brown J., Lee M. R. Studies with fenoldopam, a dopamine receptor DA1 agonist, in essential hypertension. Br J Clin Pharmacol. 1986 Jan;21(1):53–61. doi: 10.1111/j.1365-2125.1986.tb02822.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hieble J. P., Owen D. A., Harvey C. A., Blumberg A. L., Valocik R. E., DeMarinis R. M. Hemodynamic effects of selective dopamine receptor agonists in the rat and dog. Clin Exp Hypertens A. 1987;9(5-6):889–912. doi: 10.3109/10641968709161456. [DOI] [PubMed] [Google Scholar]
  11. Lacković Z., Relja M. Evidence for a widely distributed peripheral dopaminergic system. Fed Proc. 1983 Oct;42(13):3000–3004. [PubMed] [Google Scholar]
  12. Lefèvre-Borg F., Lorrain J., Lechaire J., Thiry C., Hicks P. E., Cavero I. Studies on the mechanisms of the development of tolerance to the hypotensive effects of fenoldopam in rats. J Cardiovasc Pharmacol. 1988 Apr;11(4):444–455. doi: 10.1097/00005344-198804000-00010. [DOI] [PubMed] [Google Scholar]
  13. Lombardi C., De Cotiis R., Spedini C., Missale C., Memo M., Spano P. F. Reversal by the selective D-2 dopamine receptor blocker sulpiride of the hypotensive effect of co-dergocrine in elderly hypertensives. Eur J Clin Pharmacol. 1987;33(5):519–521. doi: 10.1007/BF00544247. [DOI] [PubMed] [Google Scholar]
  14. Malchoff C. D., Hughes J. M., Carey R. M. Effect of upright posture on the aldosterone responses to dopamine, metoclopramide, angiotensin II, and adrenocorticotropin. J Clin Endocrinol Metab. 1987 Jul;65(1):203–207. doi: 10.1210/jcem-65-1-203. [DOI] [PubMed] [Google Scholar]
  15. McCarty R., Kirby R. F., Carey R. M. Dopamine may be a neurohormone in rat adrenal cortex. Am J Physiol. 1984 Dec;247(6 Pt 1):E709–E713. doi: 10.1152/ajpendo.1984.247.6.E709. [DOI] [PubMed] [Google Scholar]
  16. Murphy M. B., McCoy C. E., Weber R. R., Frederickson E. D., Douglas F. L., Goldberg L. I. Augmentation of renal blood flow and sodium excretion in hypertensive patients during blood pressure reduction by intravenous administration of the dopamine1 agonist fenoldopam. Circulation. 1987 Dec;76(6):1312–1318. doi: 10.1161/01.cir.76.6.1312. [DOI] [PubMed] [Google Scholar]
  17. Nagahama S., Chen Y. F., Lindheimer M. D., Oparil S. Mechanism of the depressor action of LY171555, a selective dopamine D2 receptor agonist, in the anesthetized rat. J Pharmacol Exp Ther. 1986 Nov;239(2):426–432. [PubMed] [Google Scholar]
  18. Nagahama S., Chen Y. F., Lindheimer M. D., Oparil S. Mechanism of the pressor action of LY171555, a specific dopamine D2 receptor agonist, in the conscious rat. J Pharmacol Exp Ther. 1986 Mar;236(3):735–742. [PubMed] [Google Scholar]
  19. Ruilope L. M., Robles R. G., Miranda B., Tovar J., Alcazar J. M., Sancho J., Rodicio J. L., Martinez A., Astorga A., Beck T. Renal effects of fenoldopam in refractory hypertension. J Hypertens. 1988 Aug;6(8):665–669. doi: 10.1097/00004872-198808000-00010. [DOI] [PubMed] [Google Scholar]
  20. Swagzdis J. E., Wittendorf R. W., DeMarinis R. M., Mico B. A. Pharmacokinetics of dopamine-2 agonists in rats and dogs. J Pharm Sci. 1986 Oct;75(10):925–928. doi: 10.1002/jps.2600751002. [DOI] [PubMed] [Google Scholar]
  21. Vallar L., Meldolesi J. Mechanisms of signal transduction at the dopamine D2 receptor. Trends Pharmacol Sci. 1989 Feb;10(2):74–77. doi: 10.1016/0165-6147(89)90082-5. [DOI] [PubMed] [Google Scholar]
  22. White W. B., Radford M. J., Gonzalez F. M., Weed S. G., McCabe E. J., Katz A. M. Selective dopamine-1 agonist therapy in severe hypertension: effects of intravenous fenoldopam. J Am Coll Cardiol. 1988 May;11(5):1118–1123. doi: 10.1016/s0735-1097(98)90073-0. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES