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. 1984 Dec;74(6):2198–2207. doi: 10.1172/JCI111646

Selective peripheral dopamine-1 receptor stimulation with fenoldopam in human essential hypertension.

R M Carey, R M Stote, J W Dubb, L H Townsend, C E Rose Jr, D L Kaiser
PMCID: PMC425412  PMID: 6150942

Abstract

SKF 82526-J, or fenoldopam, a benzazepine derivative, is a selective dopamine-1 (DA-1) agonist devoid of activity at dopamine-2, alpha- or beta-adrenergic receptors. We studied SKF 82526-J in 10 patients with essential hypertension and five normal control subjects on constant 150-meq sodium, 60 meq potassium intake. In the hypertensive patients, during a 6-d placebo period supine blood pressure and heart rate were stable at 156 +/- 6/105 +/- 4 mmHg and 76 +/- 5 beats/min, respectively. In response to a single oral dose of 100 mg of SKF 82526-J, supine blood pressure decreased to a nadir of 141 +/- 5/89 +/- 8 mmHg (P less than 0.0001) at 90 min and remained decreased at 145 +/- 6/99 +/- 3 mmHg (P less than 0.0001) at 4 h. Heart rate increased to 91 +/- 5 beats/min (P less than 0.002), but returned to control levels (82 +/- 5 beats/min) at 4 h. Renal blood flow increased from 371 +/- 57 to a peak of 659 +/- 104 ml/min and renal vascular resistance fell from 34 +/- 5 to 19 +/- 2 dyn sec cm-5 X 10(3) (P less than 0.01). Urine volume, sodium and fractional sodium excretion, and plasma renin activity were increased as a result of SKF 82526-J administration. During the ensuing 3 wk of SKF 82526-J, blood pressure remained decreased and returned to control levels after placebo administration. In contrast, in normal subjects SKF 82526-J administration was associated with a small transient reduction in diastolic pressure only. These results suggest that reduced dopaminergic activity expressed at the peripheral DA-1 receptor may contribute to the pathophysiology and/or maintenance of increased blood pressure in essential hypertension. In addition, the results suggest that peripheral DA-1 receptor stimulation with SKF 82526-J may be efficacious in the treatment of human essential hypertension.

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Selected References

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  1. Ackerman D. M., Blumberg A. L., McCafferty J. P., Sherman S. S., Weinstock J., Kaiser C., Berkowitz B. Potential usefulness of renal vasodilators in hypertension and renal disease: SK&F 82526. Fed Proc. 1983 Feb;42(2):186–190. [PubMed] [Google Scholar]
  2. BROD J., FENCL V., HEJL Z., JIRKA J., ULRYCH M. General and regional haemodynamic pattern underlying essential hypertension. Clin Sci. 1962 Oct;23:339–349. [PubMed] [Google Scholar]
  3. BRUN C. A rapid method for the determination of para-aminohippuric acid in kidney function tests. J Lab Clin Med. 1951 Jun;37(6):955–958. [PubMed] [Google Scholar]
  4. Carey R. M., Thorner M. O., Ortt E. M. Dopaminergic inhibition of metoclopramide-induced aldosterone secretion in man. Dissociation of responses to dopamine and bromocriptine. J Clin Invest. 1980 Jul;66(1):10–18. doi: 10.1172/JCI109822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carey R. M., Thorner M. O., Ortt E. M. Effects of metoclopramide and bromocriptine on the renin-angiotensin-aldosterone system in man. Dopaminergic control of aldosterone. J Clin Invest. 1979 Apr;63(4):727–735. doi: 10.1172/JCI109356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Drake C. R., Jr, Ragsdale N. V., Kaiser D. L., Carey R. M. Dopaminergic suppression of angiotensin II-induced aldosterone secretion in man: differential responses during sodium loading and depletion. Metabolism. 1984 Aug;33(8):696–702. doi: 10.1016/0026-0495(84)90207-5. [DOI] [PubMed] [Google Scholar]
  7. Edwards R. M. Segmental effects of norepinephrine and angiotensin II on isolated renal microvessels. Am J Physiol. 1983 May;244(5):F526–F534. doi: 10.1152/ajprenal.1983.244.5.F526. [DOI] [PubMed] [Google Scholar]
  8. Foster L. B., Dunn R. T. Single-antibody technique for radioimmunoassay of cortisol in unextracted serum or plasma. Clin Chem. 1974 Mar;20(3):365–368. [PubMed] [Google Scholar]
  9. Goldberg L. I. Cardiovascular and renal actions of dopamine: potential clinical applications. Pharmacol Rev. 1972 Mar;24(1):1–29. [PubMed] [Google Scholar]
  10. Goldberg L. I. Vascular dopamine receptor as a model for other dopamine receptors. Adv Biochem Psychopharmacol. 1978;19:119–129. [PubMed] [Google Scholar]
  11. Goldberg L. I., Volkman P. H., Kohli J. D. A comparison of the vascular dopamine receptor with other dopamine receptors. Annu Rev Pharmacol Toxicol. 1978;18:57–79. doi: 10.1146/annurev.pa.18.040178.000421. [DOI] [PubMed] [Google Scholar]
  12. Guyton A. C., Granger H. J., Coleman T. G. Autoregulation of the total systemic circulation and its relation to control of cardiac output and arterial pressure. Circ Res. 1971 Jan;28(Suppl):93–97. [PubMed] [Google Scholar]
  13. HEYROVSKY A. A new method for the determination of inulin in plasma and urine. Clin Chim Acta. 1956 Sep-Oct;1(5):470–474. doi: 10.1016/0009-8981(56)90020-1. [DOI] [PubMed] [Google Scholar]
  14. Hahn R. A., Wardell J. R., Jr, Sarau H. M., Ridley P. T. Characterization of the peripheral and central effects of SK&F 82526, a novel dopamine receptor agonist. J Pharmacol Exp Ther. 1982 Nov;223(2):305–313. [PubMed] [Google Scholar]
  15. Hollenberg N. K., Adams D. F., Solomon H., Chenitz W. R., Burger B. M., Abrams H. L., Merrill J. P. Renal vascular tone in essential and secondary hypertension: hemodynamic and angiographic responses to vasodilators. Medicine (Baltimore) 1975 Jan;54(1):29–44. doi: 10.1097/00005792-197501000-00002. [DOI] [PubMed] [Google Scholar]
  16. Hollenberg N. K., Borucki L. J., Adams D. F. The renal vasculature in early essential hypertension: evidence for a pathogenetic role. Medicine (Baltimore) 1978 Mar;57(2):167–178. doi: 10.1097/00005792-197803000-00004. [DOI] [PubMed] [Google Scholar]
  17. Johns D. W., Ayers C. R., Carey R. M. The dopamine agonist bromocriptine induces hypotension by venous and arteriolar dilation. J Cardiovasc Pharmacol. 1984 Jul-Aug;6(4):582–587. doi: 10.1097/00005344-198407000-00005. [DOI] [PubMed] [Google Scholar]
  18. Kebabian J. W., Calne D. B. Multiple receptors for dopamine. Nature. 1979 Jan 11;277(5692):93–96. doi: 10.1038/277093a0. [DOI] [PubMed] [Google Scholar]
  19. Kolloch R., Kobayashi K., DeQuattro V. Dopaminergic control of sympathetic tone and blood pressure: evidence in primary hypertension. Hypertension. 1980 Jul-Aug;2(4):390–394. doi: 10.1161/01.hyp.2.4.390. [DOI] [PubMed] [Google Scholar]
  20. MCDONALD R. H., Jr, GOLDBERG L. I., MCNAY J. L., TUTTLE E. P., Jr EFFECT OF DOPAMINE IN MAN: AUGMENTATION OF SODIUM EXCRETION, GLOMERULAR FILTRATION RATE, AND RENAL PLASMA FLOW. J Clin Invest. 1964 Jun;43:1116–1124. doi: 10.1172/JCI104996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mizoguchi H., Dzau V. J., Siwek L. G., Barger A. C. Effect of intrarenal administration of dopamine on renin release in conscious dogs. Am J Physiol. 1983 Jan;244(1):H39–H45. doi: 10.1152/ajpheart.1983.244.1.H39. [DOI] [PubMed] [Google Scholar]
  22. Reubi F. C., Weidmann P., Hodler J., Cottier P. T. Changes in renal function in essential hypertension. Am J Med. 1978 Apr;64(4):556–563. doi: 10.1016/0002-9343(78)90573-9. [DOI] [PubMed] [Google Scholar]
  23. Sinha Y. N., Selby F. W., Lewis U. J., VanderLaan W. P. A homologous radioimmunoassay for human prolactin. J Clin Endocrinol Metab. 1973 Mar;36(3):509–516. doi: 10.1210/jcem-36-3-509. [DOI] [PubMed] [Google Scholar]
  24. Stote R. M., Dubb J. W., Familiar R. G., Erb B. B., Alexander F. A new oral renal vasodilator, fenoldopam. Clin Pharmacol Ther. 1983 Sep;34(3):309–315. doi: 10.1038/clpt.1983.173. [DOI] [PubMed] [Google Scholar]
  25. Weinstock J., Wilson J. W., Ladd D. L., Brush C. K., Pfeiffer F. R., Kuo G. Y., Holden K. G., Yim N. C., Hahn R. A., Wardell J. R., Jr Separation of potent central and renal dopamine agonist activity in substituted 6-chloro-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepines. J Med Chem. 1980 Sep;23(9):973–975. doi: 10.1021/jm00183a001. [DOI] [PubMed] [Google Scholar]
  26. Whitfield L., Sowers J. R., Tuck M. L., Golub M. S. Dopaminergic control of plasma catecholamine and aldosterone responses to acute stimuli in normal man. J Clin Endocrinol Metab. 1980 Oct;51(4):724–729. doi: 10.1210/jcem-51-4-724. [DOI] [PubMed] [Google Scholar]

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