Skip to main content
Log in

Interstitial noradrenaline concentration of rat hearts as influenced by cellular catecholamine uptake mechanisms

  • Part I: Cardiac Development and Regulation
  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Marked concentration differences of noradrenaline (NA) between the vascular and the interstitial compartment were detected by sampling interstitial transudate from isolated perfused rat hearts. The ratios of vascular/interstitial concentration amounted to 7.4 to 1.3 depending on the concentration of NA administered (3 × 10−9 to 10−6 M). These concentration differences were abolished by inhibitors of uptake1 desipramine (DMI) I and uptake, (O-methyl-isoprenaline (OMI)). Neuronal uptake, was characterized by a Km of 0.22 μmol/l and a Vmax of 370 pmol × min−1 × gWWT−1, extraneuronal uptake2 by a KUPTAKE of = 0.313 min−4.

The apparent permeability surface area (P×S)-product calculated from uptake rate and transcapillary concentration difference was significantly decreased by administrating 100 μmol/l (NA) in presence of DMI. A presumed endothelial uptake mechanism contributing to catecholamine translocation was investigated in endothelial cells in culture. These cells showed a specific noradrenaline uptake with a Km of 4.35 μmol/l and a Vmax of about 75 pmol × min−1 x gWWT−1. Any inhibiton by inhibitors of both of the two noradrenaline uptakes was lacking. The uptake rate of this mechanism is insufficient to contribute to the diffusive conductivity of the capillary wall (P × S-product). We conclude from our investigations on interstitial concentrations of catecholamines and transcapillary concentration differences, that the capillary wall, owing to its metabolic and diffusional characteristics, influences the exchange of catecholamines to a substantial and physiologically relevant extent.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Silverberg AB, Shah SD, Haymond MW, Cryer PE: Norepinephrine: hormone and neurotransmitter in man. Am J Physiol 234: E252-E256, 1978

    PubMed  Google Scholar 

  2. Cousineau D, Goresky CA, Bach GG, Rose CP: In vivo norepinephrine dynamics in the heart. In: G.E. Mann and D.L. Yudilevich (eds.). Carrier mediated transport of solutes from blood to tissue, 1985, pp 139–153

  3. Henseling M: The role of neuronal and extraneuronal uptake in the inactivation of 3H-(−)noradrenaline in the rabbit aorta determined by a method relating uptake with amine diffusion in the tissue. NaunynSchmiedeberg's Arch Pharmacol 324: 163–168, 1983

    Google Scholar 

  4. Kammermeier H, Wendtland B: Interstitial fluid of isolated perfused rat hearts: glucose and lactate concentration. J Mol Cell Cardiol 19: 167–175, 1987

    PubMed  Google Scholar 

  5. Wienen W, Kammermeier H: Intra- and extracellular marker in the interstitial transudate of perfused rat heart. Am J Physiol 245: H785-H794, 1988

    Google Scholar 

  6. Decking U, Jüngling E, Kammermeier H: Interstitial transudate concentration of adenosine and inosine in rat and guinea pig hearts. Am J Physiol 254: 1125–1132, 1988

    Google Scholar 

  7. Iversen LL: The uptake of noradrenaline by the isolated perfused rat heart. Brit J Pharmacol 21: 523–537, 1963

    Google Scholar 

  8. Iversen LL: The uptake of catecholamine at high perfusion concentrataions in the rat isolated heart: a novel catecholamine uptake process. Brit J Pharmacol 25: 18–33, 1965

    Google Scholar 

  9. Linssen MCJG, Vork MM, De Jong YF, Glatz JFC, Van der Vusse GJ: Fatty acid-oxidation capacity and fatty acid-binding protein content of different cell types isolated from rat heart. Mol Cell Biochem 98: 19–26, 1990

    Article  PubMed  Google Scholar 

  10. Trendelenburg U: Extraneuronal uptake and metabolism of catecholamines. In: U. Trendelenburg, N. Weiner (eds.). Handbook of Experimental Pharmacology 90/I ‘Catecholamines’, Springer, Berlin, 1988, pp 279–319

    Google Scholar 

  11. Bradford M: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254, 1976

    Article  CAS  PubMed  Google Scholar 

  12. Grohmann M, Trendelenburg U: The substrate specifity of uptake, in the rat heart. Naunyn-Schmiedeberg's Arch Pharm 328: 164–173, 1984

    Google Scholar 

  13. Taylor AE, Gibson WH, Granger HJ, Guyton AC: The interaction between intracapillary and tissue forces in the overall regulation of interstitial fluid volume. Lymphology 6: 192–208, 1973

    PubMed  Google Scholar 

  14. Graefe KH, Bönisch H: The transport of amines across the axonal membranes of noradrenergic and dopaminergic neurones. In: U. Trendelenburg, N. Weiner (eds.). Handbook of Experimental Pharmacology 90/I ‘Catecholamines’, Springer, Berlin, 1988, pp 193–246

    Google Scholar 

  15. Peronnet F, Nadeau RA, De Champlain J, Imbach A, Cousineau D: Etude de la response sympathique a l'exercise chez le chien normal et après blocage de recepteurs adrenergiques beta (abstr). Proc Int Union Physiol Sci 13: 588, 1977

    Google Scholar 

  16. Scriven AJI, Dollery CT, Murphy MB, Macquin I, Brown MJ: Blood pressure and plasma norepinephrine concentrations after endogenous norepinephrine release by tyramine. Clin Pharmacol Ter 33: 710–716, 1983

    Google Scholar 

  17. Lightman SL, Iversen LL: The role of uptake, in the extraneuronal metabolism of catecholamines in the isolated rat heart. Brit J Pharmacol 37: 638–649, 1969

    Google Scholar 

  18. Aukland K, Fadnes HO: Protein concentration of interstitial fluid collected from rat skin by a wick method. Acta Phys Scand Suppl 463: 111–122, 1973

    Google Scholar 

  19. Hanley F, Messina LM, Baer RW Uhlig PN, Hoffmann JIE: Direct measurement of left ventricular interstitial adenosine. Am J Physiol 245: 11327–11335, 1983

    Google Scholar 

  20. Crone C, Levitt DG: Capillary permeability to small molecules. In: EM Fenkin and CC Michel (eds). Handbook Physiology, Section 2, The cardiovascular system. Am Physiol Soc, Bethesda.

  21. Hughes J, Gillis CN, Bloom FE: The uptake and disposition of dinorepinephrine in perfused rat lung. J Pharmacol Exp Ther 169: 237–248, 1969

    PubMed  Google Scholar 

  22. Nicholas TE, Strum JM, Angelo LS, Junod AF: Site and mechanism of 3H-/-norepinephrine by isolated perfused rat lungs. Circ Res 35: 670–680, 1974

    PubMed  Google Scholar 

  23. Nees S, Herzog V, Becker B, Boeck M, Des Rosiers Ch, Gerlach E: The coronary endothelium a highly active metabolic barrier for adenosine. Basic Res Cardiol 80: 515–529, 1985

    PubMed  Google Scholar 

  24. Anversa P, Olivetti G, Melissari M, Loud AV: Stereological measurement of cellular hypertrophy and hyperplasia in the papillary muscle of adult rat. J Mol Cell Cardiol 12: 781–795, 1980

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Obst, O.O., Linssen, M.C.J.G., Vusse, G.J.v.d. et al. Interstitial noradrenaline concentration of rat hearts as influenced by cellular catecholamine uptake mechanisms. Mol Cell Biochem 163, 173–180 (1996). https://doi.org/10.1007/BF00408655

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00408655

Key words

Navigation