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. 1968 Oct;47(10):2359–2373. doi: 10.1172/JCI105920

Catecholamine turnover in normotensive and hypertensive man: effects of antiadrenergic drugs

Vincent DeQuattro 1, Albert Sjoerdsma 1
PMCID: PMC297399  PMID: 5676529

Abstract

Intravenous administration of tritium-labeled 3,4-dihydroxyphenylalanine (dopa) to human subjects resulted in the labeling of endogenous catecholamines and vanillylmandelic acid (VMA). Determination of the changes in specific activity of these compounds with time in fractional collections of urine and in cardiac biopsies from patients undergoing corrective cardiac surgery permitted estimation of apparent turnover rates. The average half-time of the exponential decline in specific activity of labeled urinary norepinephrine was about 8 hr and that of VMA was 11-16 hr in five normal subjects. No significant differences from normal were observed in eight patients with essential hypertension. The average half-life of norepinephrine was only 5 hr in cardiac patients undergoing surgery, and the levels and rate of decline of cardiac norepinephrine specific activity correlated well with the exponential phase of the urinary disappearance curve. There were significant effects of treatment with alpha-methyltyrosine, reserpine, and pargyline hydrochloride on the labeling and apparent turnover rates of norepinephrine and VMA; the effects noted were consistent with known actions of these three drugs. It is suggested that the technique used is a suitable means of assessing “over-all” catecholamine metabolism in man, particulary if combined with quantitative assay of urinary catecholamine metabolites.

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Selected References

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

  1. BERTLER A., CARLSSON A., ROSENGREN E. A method for the fluorimetric determination of adrenaline and noradrenaline in tissues. Acta Physiol Scand. 1958 Dec 15;44(3-4):273–292. doi: 10.1111/j.1748-1716.1958.tb01627.x. [DOI] [PubMed] [Google Scholar]
  2. BRUNJES S. CATECHOL AMINE METABOLISM IN ESSENTIAL HYPERTENSION. N Engl J Med. 1964 Jul 16;271:120–124. doi: 10.1056/NEJM196407162710303. [DOI] [PubMed] [Google Scholar]
  3. BRUNJES S., HAYWOOD L. J., MARONDE R. F. A controlled study of the antihypertensive response to an MAO inhibitor. B. Urinary excretion of catecholamines and their metabolites. Ann N Y Acad Sci. 1963 Jul 8;107:982–992. doi: 10.1111/j.1749-6632.1963.tb13342.x. [DOI] [PubMed] [Google Scholar]
  4. Bertler A., Falck B., Owman C., Rosengrenn E. The localization of monoaminergic blood-brain barrier mechanisms. Pharmacol Rev. 1966 Mar;18(1):369–385. [PubMed] [Google Scholar]
  5. Bertler A., Rosengren E. Possible role of brain dopamine. Pharmacol Rev. 1966 Mar;18(1):769–773. [PubMed] [Google Scholar]
  6. Blum J. J., Kirshner N., Utley J. The effect of reserpine on growth and catecholamine content of Tetrahymena. Mol Pharmacol. 1966 Nov;2(6):606–608. [PubMed] [Google Scholar]
  7. CHIDSEY C. A., BRAUNWALD E., MORROW A. G., MASON D. T. MYOCARDIAL NOREPINEPHRINE CONCENTRATION IN MAN. EFFECTS OF RESERPINE AND OF CONGESTIVE HEART FAILURE. N Engl J Med. 1963 Sep 26;269:653–658. doi: 10.1056/NEJM196309262691302. [DOI] [PubMed] [Google Scholar]
  8. Carlsson A. Modification of sympathetic function. Pharmacological depletion of catecholamine stores. Pharmacol Rev. 1966 Mar;18(1):541–549. [PubMed] [Google Scholar]
  9. Chidsey C. A., Braunwald E. Sympathetic activity and neurotransmitter depletion in congestive heart failure. Pharmacol Rev. 1966 Mar;18(1):685–700. [PubMed] [Google Scholar]
  10. DOYLE A. E., FRASER J. R. Vascular reactivity in hypertension. Circ Res. 1961 May;9:755–761. doi: 10.1161/01.res.9.3.755. [DOI] [PubMed] [Google Scholar]
  11. DRUJAN B. D., SOURKES T. L., LAYNE D. S., MURPHY G. F. The differential determination of catecholamines in urine. Can J Biochem Physiol. 1959 Oct;37:1153–1159. [PubMed] [Google Scholar]
  12. Engelman K., Horwitz D., Jéquier E., Sjoerdsma A. Biochemical and pharmacologic effects of alpha-methyltyrosine in man. J Clin Invest. 1968 Mar;47(3):577–594. doi: 10.1172/JCI105754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. GITLOW S. E., MENDLOWITZ M., WILK E. K., WILK S., WOLF R. L., NAFTCHI N. E. PLASMA CLEARANCE OF DL-BETA-H3-NOREPINEPHRINE IN NORMAL HUMAN SUBJECTS AND PATIENTS WITH ESSENTIAL HYPERTENSION. J Clin Invest. 1964 Oct;43:2009–2015. doi: 10.1172/JCI105075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gey K. F., Pletscher A. Distribution and metabolism of DL-3,4-dihydroxy[2-14C]-phenylalanine in rat tissues. Biochem J. 1964 Aug;92(2):300–308. doi: 10.1042/bj0920300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gordon R., Spector S., Sjoerdsma A., Udenfriend S. Increased synthesis of norepinephrine and epinephrine in the intact rat during exercise and exposure to cold. J Pharmacol Exp Ther. 1966 Sep;153(3):440–447. [PubMed] [Google Scholar]
  16. HERTTING G., AXELROD J. Fate of tritiated noradrenaline at the sympathetic nerve-endings. Nature. 1961 Oct 14;192:172–173. doi: 10.1038/192172a0. [DOI] [PubMed] [Google Scholar]
  17. Ikoma T. Studies on catechols with reference to hypertension. I. Jpn Circ J. 1965 Dec;29(12):1269–1277. doi: 10.1253/jcj.29.1269. [DOI] [PubMed] [Google Scholar]
  18. KOPIN I. J., GORDON E. K. Metabolism of norepinephrine-H3 released by tyramine and reserpine. J Pharmacol Exp Ther. 1962 Dec;138:351–359. [PubMed] [Google Scholar]
  19. KOPIN I. J. STORAGE AND METABOLISM OF CATECHOLAMINES: THE ROLE OF MONOAMINE OXIDASE. Pharmacol Rev. 1964 Jun;16:179–191. [PubMed] [Google Scholar]
  20. Krakoff L. R., de Champlain J., Axelrod J. Abnormal storage of norepinephrine in experimental hypertension in the rat. Circ Res. 1967 Nov;21(5):583–591. doi: 10.1161/01.res.21.5.583. [DOI] [PubMed] [Google Scholar]
  21. LOVENBERG W., WEISSBACH H., UDENFRIEND S. Aromatic L-amino acid decarboxylase. J Biol Chem. 1962 Jan;237:89–93. [PubMed] [Google Scholar]
  22. MENDLOWITZ M., GITLOW S., NAFTCHI N. Work of digital vasoconstriction produced by infused norepinephrine in Cushing's syndrome. J Appl Physiol. 1958 Sep;13(2):252–256. doi: 10.1152/jappl.1958.13.2.252. [DOI] [PubMed] [Google Scholar]
  23. Neff N. H., Costa E. The influence of monoamine oxidase inhibition on catecholamine synthesis. Life Sci. 1966 May;5(10):951–959. doi: 10.1016/0024-3205(66)90204-9. [DOI] [PubMed] [Google Scholar]
  24. Overy H. R., Pfister R., Chidsey C. A. Studies on the renal excretion of norepinephrine. J Clin Invest. 1967 Apr;46(4):482–489. doi: 10.1172/JCI105550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. PISANO J. J. A simple analysis for normetanephrine and metanephrine in urine. Clin Chim Acta. 1960 May;5:406–414. doi: 10.1016/0009-8981(60)90146-7. [DOI] [PubMed] [Google Scholar]
  26. PISANO J. J., CROUT J. R., ABRAHAM D. Determination of 3-methoxy-4-hydroxymandelic acid in urine. Clin Chim Acta. 1962 Mar;7:285–291. doi: 10.1016/0009-8981(62)90022-0. [DOI] [PubMed] [Google Scholar]
  27. Pletscher A. Monoamine oxidase inhibitors. Pharmacol Rev. 1966 Mar;18(1):121–129. [PubMed] [Google Scholar]
  28. SJOERDSMA A., LEEPER L. C., TERRY L. L., UDENFRIEND S. Studies on the biogenesis and metabolism of norepinephrine in patients with pheochromocytoma. J Clin Invest. 1959 Jan 1;38(1 Pt 1):31–38. doi: 10.1172/JCI103793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. SPECTOR S., SJOERDSMA A., UDENFRIEND S. BLOCKADE OF ENDOGENOUS NOREPINEPHRINE SYNTHESIS BY ALPHA-METHYL-TYROSINE, AN INHIBITOR OF TYROSINE HYDROXYLASE. J Pharmacol Exp Ther. 1965 Jan;147:86–95. [PubMed] [Google Scholar]
  30. Sjoerdsma A., Engelman K., Spector S., Udenfriend S. Inhibition of catecholamine synthesis in man with alpha-methyl-tyrosine, an inhibitor of tyrosine hydroxylase. Lancet. 1965 Nov 27;2(7422):1092–1094. doi: 10.1016/s0140-6736(65)90062-0. [DOI] [PubMed] [Google Scholar]
  31. Spector S., Gordon R., Sjoerdsma A., Udenfriend S. End-product inhibition of tyrosine hydroxylase as a possible mechanism for regulation of norepinephrine synthesis. Mol Pharmacol. 1967 Nov;3(6):549–555. [PubMed] [Google Scholar]
  32. Stott A. W., Robinson R. Urinary normetadrenaline excretion in essential hypertension. Clin Chim Acta. 1967 May;16(2):249–252. doi: 10.1016/0009-8981(67)90188-x. [DOI] [PubMed] [Google Scholar]
  33. UDENFRIEND S., ZALTZMAN-NIRENBERG P. NOREPINEPHRINE AND 3,4DIHYDROXYPHENETHYLAMINE TURNOVER IN GUINEA PIG BRAIN IN VIVO. Science. 1963 Oct 18;142(3590):394–396. doi: 10.1126/science.142.3590.394. [DOI] [PubMed] [Google Scholar]
  34. WEGMANN A. DETERMINATION OF 3-HYDROXYTYRAMINE AND DOPA IN VARIOUS ORGANS OF DOG AFTER DOPA-INFUSION. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1963 Nov 8;246:184–190. doi: 10.1007/BF00245004. [DOI] [PubMed] [Google Scholar]
  35. de Champlain J., Krakoff L. R., Axelrod J. Catecholamine metabolism in experimental hypertension in the rat. Circ Res. 1967 Jan;20(1):136–145. doi: 10.1161/01.res.20.1.136. [DOI] [PubMed] [Google Scholar]

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