Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1979 Nov;64(5):1221–1228. doi: 10.1172/JCI109576

Vascular and metabolic effects of circulating epinephrine and norepinephrine. Concentration-effect study in dogs.

P Hjemdahl, E Belfrage, M Daleskog
PMCID: PMC371267  PMID: 227927

Abstract

Vascular and metabolic effects of circulating epinephrine and norepinephrine have been studied in relation to the plasma concentration of these amines in dogs. Intravenous infusion of epinephrine or norepinephrine (0.1, 0.5, and 2.5 nmol x kg-1 x min-1) raised the plasma concentration of the infused amine by 2.5 , 13, and 63 nM from resting levels of 2.4 and 3.6 nM, respectively. Blood flow to isolated adipose tissue; skeletal muscle preparations; and plasma levels of glycerol, glucose, and cyclic AMP were measured. Epinephrine and norepinephrine displayed a distinct selectivity with regard to both vascular and metabolic effects. Epinephrine caused significant vasoconstriction in adipose tissue already at a plasma concentration of 5 nM, whereas no significant effect was seen on skeletal muscle vascular resistance. Norepinephrine, on the other hand, caused significant vasoconstriction in skeletal muscle at 5 nM but had no vasoconstrictor effect in adipose tissue. Epinephrine was more potent than norepinephrine in increasing plasma cyclic AMP and glucose, whereas the converse was true for plasma glycerol. Epinephrine had significant effects on plasma cyclic AMP at 5 nM and on plasma glucose and glycerol at 15 nM. Norepinephrine, on the other hand, had significant effects on plasma glycerol at 5 nM, plasma cyclic AMP at 15 nM and plasma glucose only at 65 nM. It is suggested that these response patterns are related to a preferential action of epinephrine on beta 2-adrenoceptors and a preferential action of norepinephrine on beta 1-adrenoceptors. Our results support the view that both epinephrine and norepinephrine may act as circulating hormones, because vascular and metabolic effects of both amines were seen at plasma concentrations encountered during various kinds of stress in animals and man.

Full text

PDF
1223

Selected References

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

  1. Axelrod J., Weinshilboum R. Catecholamines. N Engl J Med. 1972 Aug 3;287(5):237–242. doi: 10.1056/NEJM197208032870508. [DOI] [PubMed] [Google Scholar]
  2. Ball J. H., Kaminsky N. I., Hardman J. G., Broadus A. E., Sutherland E. W., Liddle G. W. Effects of catecholamines and adrenergic-blocking agents on plasma and urinary cyclic nucleotides in man. J Clin Invest. 1972 Aug;51(8):2124–2129. doi: 10.1172/JCI107019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ballard K. Blood flow in canine adipose tissue during intravenous infusion of norepinephrine. Am J Physiol. 1973 Nov;225(5):1026–1031. doi: 10.1152/ajplegacy.1973.225.5.1026. [DOI] [PubMed] [Google Scholar]
  4. Belfrage E. Comparison of beta-adrenoceptors mediating vasodilatation in canine subcutaneous adipose tissue and skeletal muscle. Acta Physiol Scand. 1978 Apr;102(4):469–476. doi: 10.1111/j.1748-1716.1978.tb06095.x. [DOI] [PubMed] [Google Scholar]
  5. Belfrage E. Vasodilatation and modulation of vasoconstriction in canine subcutaneous adipose tissue caused by activation of beta-adrenoceptors. Acta Physiol Scand. 1978 Apr;102(4):459–468. doi: 10.1111/j.1748-1716.1978.tb06094.x. [DOI] [PubMed] [Google Scholar]
  6. Broadus A. E. Clinical cyclic nucleotide research. Adv Cyclic Nucleotide Res. 1977;8:509–548. [PubMed] [Google Scholar]
  7. Brown B. L., Ekins R. P., Albano J. D. Saturation assay for cyclic AMP using endogenous binding protein. Adv Cyclic Nucleotide Res. 1972;2:25–40. [PubMed] [Google Scholar]
  8. Bühler H. U., da Prada M., Haefely W., Picotti G. B. Plasma adrenaline, noradrenaline and dopamine in man and different animal species. J Physiol. 1978 Mar;276:311–320. doi: 10.1113/jphysiol.1978.sp012235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Carlström S., Westling H. Metabolic, circulatory and respiratory effects of a new sympathomimetic beta-receptor-stimulating agent, terbutaline, compared with those of orciprenaline. Acta Med Scand Suppl. 1970;512:33–40. doi: 10.1111/j.0954-6820.1970.tb05287.x. [DOI] [PubMed] [Google Scholar]
  10. Chien S. Role of the sympathetic nervous system in hemorrhage. Physiol Rev. 1967 Apr;47(2):214–288. doi: 10.1152/physrev.1967.47.2.214. [DOI] [PubMed] [Google Scholar]
  11. Exton J. H., Harper S. C. Role of cyclic AMP in the actions of catecholamines on hepatic carbohydrate metabolism. Adv Cyclic Nucleotide Res. 1975;5:519–532. [PubMed] [Google Scholar]
  12. Farnebo L. O., Fredholm B. B., Hamberger B., Hjemdahl P., Westman L. Cyclic AMP and metabolic substrates in hemorrhagic shock of the rat. Acta Chir Scand. 1977;143(1):9–14. [PubMed] [Google Scholar]
  13. Fredholm B. B., Farnebo L. O., Hamberger B. Plasma catecholamines, cyclic AMP and metabolic substrates in hemorrhagic shock of the rat. The effect of adrenal demedullation and 6-OH-dopamine treatment. Acta Physiol Scand. 1979 Apr;105(4):481–495. doi: 10.1111/j.1748-1716.1979.tb00113.x. [DOI] [PubMed] [Google Scholar]
  14. Fredholm B. B., Lunell N. O., Persson B., Wager J. Actions of salbutamol in late pregnancy: plasma cyclic AMP, insulin and C-peptide, carbohydrate and lipid metabolites in diabetic and non-diabetic women. Diabetologia. 1978 Apr;14(4):235–242. doi: 10.1007/BF01219422. [DOI] [PubMed] [Google Scholar]
  15. Galbo H., Christensen N. J., Holst J. J. Catecholamines and pancreatic hormones during autonomic blockade in exercising man. Acta Physiol Scand. 1977 Dec;101(4):428–437. doi: 10.1111/j.1748-1716.1977.tb06026.x. [DOI] [PubMed] [Google Scholar]
  16. Galbo H., Holst J. J., Christensen N. J. Glucagon and plasma catecholamine responses to graded and prolonged exercise in man. J Appl Physiol. 1975 Jan;38(1):70–76. doi: 10.1152/jappl.1975.38.1.70. [DOI] [PubMed] [Google Scholar]
  17. Galbo H., Holst J. J., Christensen N. J., Hilsted J. Glucagon and plasma catecholamines during beta-receptor blockade in exercising man. J Appl Physiol. 1976 Jun;40(6):855–863. doi: 10.1152/jappl.1976.40.6.855. [DOI] [PubMed] [Google Scholar]
  18. Garber A. J., Cryer P. E., Santiago J. V., Haymond M. W., Pagliara A. S., Kipnis D. M. The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man. J Clin Invest. 1976 Jul;58(1):7–15. doi: 10.1172/JCI108460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Himms-Hagen J. Sympathetic regulation of metabolism. Pharmacol Rev. 1967 Sep;19(3):367–461. [PubMed] [Google Scholar]
  20. Hjemdahl P., Daleskog M., Kahan T. Determination of plasma catecholamines by high performance liquid chromatography with electrochemical detection: comparison with a radioenzymatic method. Life Sci. 1979 Jul 9;25(2):131–138. doi: 10.1016/0024-3205(79)90384-9. [DOI] [PubMed] [Google Scholar]
  21. Hjemdahl P., Fredholm B. B. Comparison of the lipolytic activity of circulating and locally released noradrenaline during acidosis. Acta Physiol Scand. 1974 Sep;92(1):1–11. doi: 10.1111/j.1748-1716.1974.tb05717.x. [DOI] [PubMed] [Google Scholar]
  22. Hjemdahl P., Fredholm B. B. Influence of acidosis on noradrenaline-induced vasoconstriction in adipose tissue and skeletal muscle. Acta Physiol Scand. 1976 Jul;97(3):319–324. doi: 10.1111/j.1748-1716.1976.tb10269.x. [DOI] [PubMed] [Google Scholar]
  23. Hjemdahl P., Fredholm B. B. Influence of adipose tissue blood flow on the lipolytic response to circulating noradrenaline at normal and reduced pH. Acta Physiol Scand. 1976 Sep;98(1):74–79. doi: 10.1111/j.1748-1716.1976.tb10304.x. [DOI] [PubMed] [Google Scholar]
  24. Hjemdahl P., Sollevi A. Vascular and metabolic responses to adrenergic stimulation in isolated canine subcutaneous adipose tissue at normal and reduced temperature. J Physiol. 1978 Aug;281:325–338. doi: 10.1113/jphysiol.1978.sp012425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hoffbrand B. I., Forsyth R. P. Regional blood flow changes during norepinephrine, tyramine and methoxamine infusions in the unanesthetized rhesus monkey. J Pharmacol Exp Ther. 1973 Mar;184(3):656–661. [PubMed] [Google Scholar]
  26. Hörtnagl H., Benedict C. R., Grahame-Smith D. G. A sensitive radioenzymatic assay for adrenaline and noradrenaline in plasma. Br J Clin Pharmacol. 1977 Oct;4(5):553–558. doi: 10.1111/j.1365-2125.1977.tb00785.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Issekutz T. B. Estimation of cyclic AMP turnover in normal and methylprednisolone-treated dogs: effect of catecholamines. Am J Physiol. 1975 Aug;229(2):291–297. doi: 10.1152/ajplegacy.1975.229.2.291. [DOI] [PubMed] [Google Scholar]
  28. Johnson D. G., Hayward J. S., Jacobs T. P., Collis M. L., Eckerson J. D., Williams R. H. Plasma norepinephrine responses of man in cold water. J Appl Physiol Respir Environ Exerc Physiol. 1977 Aug;43(2):216–220. doi: 10.1152/jappl.1977.43.2.216. [DOI] [PubMed] [Google Scholar]
  29. Lands A. M., Arnold A., McAuliff J. P., Luduena F. P., Brown T. G., Jr Differentiation of receptor systems activated by sympathomimetic amines. Nature. 1967 May 6;214(5088):597–598. doi: 10.1038/214597a0. [DOI] [PubMed] [Google Scholar]
  30. Laurell S., Tibbling G. An enzymatic fluorometric micromethod for the determination of glycerol. Clin Chim Acta. 1966 Mar;13(3):317–322. doi: 10.1016/0009-8981(66)90210-5. [DOI] [PubMed] [Google Scholar]
  31. Madsen S. N., Fog-Møller F., Christiansen C., Vester-Andersen T., Engquist A. Cyclic AMP, adrenaline and noradrenaline in plasma during surgery. Br J Surg. 1978 Mar;65(3):191–193. doi: 10.1002/bjs.1800650315. [DOI] [PubMed] [Google Scholar]
  32. Manhem P., Lecerof H., Hökfelt B. Plasma catecholamine levels in the coronary sinus, the left renal vein and peripheral vessels in healthy males at rest and during exercise. Acta Physiol Scand. 1978 Nov;104(3):364–369. doi: 10.1111/j.1748-1716.1978.tb06288.x. [DOI] [PubMed] [Google Scholar]
  33. Nielsen S. L., Lbitsch V., Larsen O. A., Lassen N. A., Quaade F. Blood flow through human adipose tissue during lipolysis. Scand J Clin Lab Invest. 1968;22(2):124–130. doi: 10.3109/00365516809160956. [DOI] [PubMed] [Google Scholar]
  34. Peuler J. D., Johnson G. A. Simultaneous single isotope radioenzymatic assay of plasma norepinephrine, epinephrine and dopamine. Life Sci. 1977 Sep 1;21(5):625–636. doi: 10.1016/0024-3205(77)90070-4. [DOI] [PubMed] [Google Scholar]
  35. Porte D., Jr, Graber A. L., Kuzuya T., Williams R. H. The effect of epinephrine on immunoreactive insulin levels in man. J Clin Invest. 1966 Feb;45(2):228–236. doi: 10.1172/JCI105335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. RENKIN E. M., ROSELL S. The influence of sympathetic adrenergic vasoconstrictor nerves on transport of diffusible solutes from blood to tissues in skeletal muscle. Acta Physiol Scand. 1962 Mar-Apr;54:223–240. doi: 10.1111/j.1748-1716.1962.tb02348.x. [DOI] [PubMed] [Google Scholar]
  37. Rosell S. Release of free fatty acids from subcutaneous adipose tissue in dogs following sympathetic nerve stimulation. Acta Physiol Scand. 1966 Jul-Aug;67(3):343–351. doi: 10.1111/j.1748-1716.1966.tb03320.x. [DOI] [PubMed] [Google Scholar]
  38. Schade D. S., Eaton R. P. The metabolic response to norepinephrine in normal versus diabetic man. Diabetologia. 1978 Dec;15(6):433–439. doi: 10.1007/BF02342866. [DOI] [PubMed] [Google Scholar]
  39. Silverberg A. B., Shah S. D., Haymond M. W., Cryer P. E. Norepinephrine: hormone and neurotransmitter in man. Am J Physiol. 1978 Mar;234(3):E252–E256. doi: 10.1152/ajpendo.1978.234.3.E252. [DOI] [PubMed] [Google Scholar]
  40. Taylor M. W., Gaddie J., Murchison L. E., Palmer K. N. Metabolic effects of oral salbutamol. Br Med J. 1976 Jan 3;1(6000):22–22. doi: 10.1136/bmj.1.6000.22. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES