Does converting enzyme inhibition change the neuronal and extraneuronal uptake of catecholamines?

  • P. Dominiak
  • A. Blöchl


In previous studies concerning the sympathetic outflow during converting enzyme inhibition, no significant changes after chronic treatment could be observed. Therefore, we investigated the effects of the long-acting converting enzyme inhibitor ramipril on the neuronal and extraneuronal uptake of SHR. Ramipril was administered either i.v. or orally to SHR, whereas desipramine or corticosterone were additionally infused to block the neuronal or extraneuronal uptake of catecholamines. As an index of sympathetic outflow, plasma noradrenaline and adrenaline concentrations were determined during preganglionic stimulation of the spinal cord using HPLC and ELCD. Blood pressure of SHR was measured in a carotid artery and was significantly decreased in the ramipril treated group under resting and stimulating conditions. Ramipril did not influence stimulated sympathetic outflow. However, in acute and chronic experiments ramipril led to an additive effect to desipramine concerning stimulated circulating catecholamines. Similar results could be obtained after blocking the uptake-2 with corticosterone. 3H-NA-uptake into the hearts of SHR was significantly diminished by about 10% after chronic ramipril administration. It is suggested that ramipril is able to decrease the neuronal and extraneuronal uptake of catecholamines by an unspecific effect due to the comparably high lipophilicity. The blood pressure lowering effect of ramipril is not supported by an inhibition of presynaptic noradrenaline release.

Key words

Converting enzyme inhibition spontaneously hypertensive rats (SHR) sympathetic outflow neuronal and extraneuronal uptake 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Berecek KH, Kirk KA, Nagahama S, Oparil S (1987) Sympathetic function in spontaneously hypertensive rats after chronic administration of captopril. Am J Physiol 252: H796 — H806PubMedGoogle Scholar
  2. 2.
    Dominiak P, Elfrath A, Türck D (1987) Effects of chronic treatment with ramipril, a new ACE blocking agent, on presynaptic sympathetic nervous system of SHR. Clin Exp Hypertens ATheor 9: 369–373CrossRefGoogle Scholar
  3. 3.
    Dominiak P, Elfrath A, Türck D (1987) Biosynthesis of catecholamines and sympathetic outflow in spontaneously hypertensive rats (SHR) after chronic treatment with CE-blocking agents. J Cardiovasc Pharmacol 10 (Supp17): S122–5124PubMedCrossRefGoogle Scholar
  4. 4.
    Erikson BM, Persson BA (1982) Determination of catecholamines in rat heart tissue and plasma samples by liquid chromatography with electrochemical detection. J Chromatogr 228: 143–154Google Scholar
  5. 5.
    Gillespie JS, Muir TC (1967) A method of stimulating the complete sympathetic outflow from the spinal cord to blood vessels in the pithed rat. Br J Pharmac Chemother 30: 78–87CrossRefGoogle Scholar
  6. 6.
    Gohlke P, Urbach H, Schölkens B, Unger Th (1989) Inhibition of converting enzyme in the cerebrospinal fluid of rats after oral treatment with converting enzyme inhibitors. J Pharmacol Exp Ther 249: 609–616PubMedGoogle Scholar
  7. 7.
    Grohmann M, Trendelenburg U (1988) The handling of five amines by the extraneuronal deaminating system of the rat heart. Naunyn-Schmiedeberg’s Arch Pharmacol 337: 159–163PubMedGoogle Scholar
  8. 8.
    Majewski H, Hedler L, Schurr C, Starke K (1984) Modulation of noradrenaline release in the pithed rabbit: a role for angiotensin II. J Cardiovasc Pharmacol 6: 888–896PubMedCrossRefGoogle Scholar
  9. 9.
    Maxwell RA, Keenan DP, Chaplin E, Roth B, Eckhardt SB (1969) Molecular features affecting the potency of tricyclic antidepressants and structurally related compounds as inhibitors of the uptake of tritiated norepinephrine by rabbit aortic strips. J Pharmacol Exp Ther 66: 320–329Google Scholar
  10. 10.
    Peach MJ (1977) Renin-angiotensin system: biochemistry and mechanism of action. Physiol Rev 57: 313–370PubMedGoogle Scholar
  11. 11.
    Schömig E, Michael-Hepp J, Bönisch H (1988) Inhibition of neuronal adrenaline uptake (uptakes) and desepramine binding by N-ethylmaleimide ( NEM ). Naunyn-Schmiedeberg’s Arch Pharmacol 337: 633–636Google Scholar
  12. 12.
    Starke K, Taube HD, Borowski E (1977) Presynaptic receptor systems in catecholaminergic transmission. Biochem Pharmacol 26: 259–268PubMedCrossRefGoogle Scholar
  13. 13.
    Trendelenburg U (1980) A kinetic analysis of the extraneuronal uptake and metabolism of catecholamines. Rev Physiol Biochem Pharmacol 87:33 ffGoogle Scholar
  14. 14.
    Trendelenburg U (1986) The metabolizing systems involved in the inactivation of catecholamines. Naunyn-Schmiedeberg’s Arch Pharmacol 332: 201–207PubMedCrossRefGoogle Scholar
  15. 15.
    Wenting GJ, Manin’t Veld AJ, Woitliez AJ, Derk FHM, Schalekamp MADH (1984) Captopril in treatment of severe acute and chronic heart failure. Progress in Pharmacology, 5/3: 107–112, Fischer Verlag, StuttgartGoogle Scholar
  16. 16.
    Xiang J-Z, Linz W, Becker H, Ganten D, Lang RE, Schölkens B, Unger Th (1985) Effects of converting enzyme inhibitors: ramipril and enalapril on peptide action and sympathetic neurotransmission in the isolated heart. Eur J Pharmacol 113: 215–223PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • P. Dominiak
    • 1
    • 3
  • A. Blöchl
    • 2
  1. 1.Department of PharmacologyMedical University of LübeckGermany
  2. 2.Department of PharmacologyUniversity of IllinoisChicagoUSA
  3. 3.Institut für Pharmakologie MedizinischeUniversität zu LübeckLübeckGermany

Personalised recommendations