Skip to main content
SpringerLink
Log in

Ergonovine-induced constrictions of epicardial coronary arteries in conscious dogs: α-adrenoceptors are not involved

  • Original Contributions
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Summary

The effect of i.v. ergonovine tartrate infusions (0.05–20 μg/kg/min, 12 minutes duration) on coronary arteries was studied in 14 conscious dogs instrumented to continuously measure vascular diameter by an ultrasonic dimension gauge using 10-MHz piezoelectric crystals.

Ergonovine induced a biphasic coronary response: small, transient dilation during the first minutes of infusion, followed by slowly developing constriction reaching its maximum 5 to 15 minutes after the end of the infusion and persisting at this level for at least 10 minutes. The threshold dosage for significant constriction was 0.05 μg/kg/min. A dosage of 5 μg/kg/min (cumulative 60 μg/kg, corresponding to 35 μg/kg ergonovine maleate) caused a decline in mean left circumflex artery diameter by 137±15 μm (=4.6%) without significantly altering heart rate, plasma catecholamines or plasma renin activity. Coronary venous O2 saturation did not decline, indicating the absence of coronary resistance vessel constriction. The epicardial artery constriction was not attenuated by a vasopressin antagonist. Under adrenergic blockade (2 mg/kg phentolamine and 2 mg/kg nadolol) or under ganglionic blockade (5 mg/kg pentolinium tartrate), ergonovine (5 μg/kg/min) caused substantial elevation in mean arterial pressure, while the decline in coronary artery diameter was attenuated. When this increase in arterial pressure was prevented by appropriate bleeding, the ergonovine-induced coronary constriction was not diminished by adrenergic or ganglionic blockade. The serotonin antagonist methysergide (0.5 mg/kg) completely abolished the ergonovine-induced coronary artery vasomotion.

It is concluded that ergonovine in dogs causes an epicardial coronary artery constriction comparable to the diffuse coronary artery narrowing in men not suffering from variant angina pectoris. These constrictions are not mediated by an adrenergic mechanism.

Zusammenfassung

Die Wirkung intravenöser Infusionen von Ergonovitartrat (0.05–20 μg/kg/min, 12 Minuten Dauer) auf die Koronararterien wurde in 14 wachen Hunden untersucht. Die Tiere waren für eine kontinuierliche Messung des Gefäßdurchmessers mit einem Ultraschall-Verfahren mittels implantierten piezoelektrischen 10-MHz-Kristallen ausgerüstet.

Ergonovin verursachte eine biphasische Koronarreaktion: eine geringgradige, vorübergehende Dilatation während der ersten Minuten der Infusion, anschließend eine allmählich einsetzende Konstriktion, die ihr Maximum erst 5–15 Minuten nach Ende der Infusion erreichte und für mindestens 10 Minuten bestehen blieb. Die Schwellendosis für signifikante Konstriktion betrug 0,05 μg/kg/min. Die Dosis von 5 μg/kg/min (kumulativ 60 μg/kg, was 35 μg/kg Ergonovin-Maleat entspricht) verursachte eine Abnahme des mittleren Durchmessers der linken umschlingenden Koronararterie um 137±15 μm (=4,6%) ohne signifikante Wirkungen auf Herzfrequenz, Plasma-Katecholamine oder Plasma-Renin-Aktivität. Die koronarvenöse O2-Sättigung nahm nicht ab, demnach erfolgte also keine Konstriktion von koronaren Widerstandsgefäßen. Die Konstriktion der epikardialen Gefäße war nicht durch einen Vasopressin-Antagonisten abschwächbar. Unter adrenerger Blockade (2 mg/kg Phentolamin und 2 mg/kg Nadolol) oder unter Ganglienblockade (5 mg/kg Pentoliniumtartrat) verursachte Ergonovin (5 μg/kg/min) eine erhebliche Zunahme des arteriellen Mitteldruckes, während die Verminderung des Koronararterien-Durchmessers abgeschwächt war. Wurde dieser arterielle Druckanstieg durch entsprechende Blutentnahme verhindert, so war die Ergonovin-induzierte Koronarkonstriktion weder durch adrenerge Blockade noch durch Ganglienblockade abgeschwächt. Der Serotonin-Antagonist Methysergid (0,5 mg/kg) hob die ergonovininduzierten Koronarreaktionen vollständig auf.

Ergonovin verursacht in Hunden eine Konstriktion epikardialer Koronararterien ähnlich der diffusen Koronarverengung in Menschen, die nicht an “Variant”-Angina-pectoris leiden. Diese Konstriktionen werden nicht durch einen adrenergen Mechanismus bewirkt.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bassenge, E., J. Holtz, C. Müller, H. Kinadeter, A. Kolin: Experimental evaluation of coronary artery vasomotion: possible significance for myocardial ischemia in coronary heart disease. Adv. Clin. Cardiol.1, 300–316 (1980).

    Google Scholar 

  2. Bassenge, E., J. Holtz, A. Kolin, G. Graser: Observations on coronary conductance artery vasomotion by induction angiometry and ultrasonic dimension technique. Basic Res. Cardiol.76, 524–529 (1981).

    PubMed  Google Scholar 

  3. Berridge, M. J.: Receptors and calcium signalling. In: Towards understanding receptors. Current reviews in biomedicine 1, Ed. J. W. Lamble, pp. 122–131 Elsevier-North Holland (Amsterdam-New York-Oxford 1981).

    Google Scholar 

  4. Brazenor, R. M., J. A. Angus: Ergometrine contracts isolated canine coronary arteries by a serotonergic mechanism: No role for alpha adrenoceptors. J. Pharmacol. Exp. Ther.218, 530–536 (1981).

    PubMed  Google Scholar 

  5. Brooke, O. G., B. F. Robinson: Effect of ergotamine and ergometrine on forearm venous compliance in man. Brit. Med. J.1970/I, 139–143.

  6. Bussmann, W.-D., W. Klug, U. Scriba, M. Kaltenbach: Wirkung von Ergonovin auf Koronarweite und Hämodynamik bei Patienten mit Angina pectoris in Ruhe. Z. Kardiol.69, 478–487 (1980).

    PubMed  Google Scholar 

  7. Buxton, A., S. Goldberg, J. W. Hirshfeld, J. Wilson, T. Mann, D. O. Williams, P. Overlie, P. Oliva: Refractory ergonovine-induced coronary vasospasm: Importance of intracoronary nitroglycerin. Amer. J. Cardiol.46, 328–334 (1980).

    Google Scholar 

  8. Cohen, M. L., R. W. Fuller, K. S. Wiley: Evidence for 5-HT2 receptors mediating contraction in vascular smooth muscle. J. Pharmacol. Exp. Ther.218, 421–425 (1981).

    PubMed  Google Scholar 

  9. Conti, C. R., R. C. Curry, Jr.: Coronary artery spasm and myocardial ischemia. Mod. Conc. Cardiovasc. Dis.49, 1–6 (1980).

    Google Scholar 

  10. Cipriano, P. R., D. F. Guthaner, A. E. Orlick, D. R. Ricci, L. Wexler, J. F. Silverman: The effects of ergonovine maleate on coronary arterial size. Circulation59, 82–89 (1979).

    PubMed  Google Scholar 

  11. Curry, R. C., Jr., C. J. Pepine, M. B. Sabom, R. L. Feldman, L. G. Christie, C. R. Conti: Effects of ergonovine in patients with and without coronary artery disease. Circulation56, 803–809 (1977).

    PubMed  Google Scholar 

  12. Ertl G., M. Fuchs: Alpha-adrenergic vasoconstriction in arterial and arteriolar sections of the canine coronary circulation. Basic Res. Cardiol.75, 600–614 (1980).

    PubMed  Google Scholar 

  13. Feldman, R. L., R. C. Curry, Jr., C. J. Pepine, J. Mehta, C. R. Conti: Regional coronary hemodynamic effects of ergonovine in patients with and without variant angina. Circulation62, 149–159 (1980).

    PubMed  Google Scholar 

  14. Fester, A.: Provocative testing for coronary arterial spasm with ergonovine maleate. Amer. J. Cardiol.46, 338–340 (1980).

    PubMed  Google Scholar 

  15. Forman R., E. S. Kirk: Comparative effects of vasodilator drugs on large and small coronary resistance vessels in the dog. Cardiovasc. Res.14, 601–606 (1980).

    PubMed  Google Scholar 

  16. Gerova, M., E. Barta, J. Gero: Sympathetic control of major coronary artery diameter in the dog. Circulat. Res.44, 459–467 (1979).

    PubMed  Google Scholar 

  17. Gunther, S., L. Green, J. E. Muller, G. H. Mudge, Jr., W. Grossmann: Inappropriate coronary vasoconstriction in patients with coronary artery disease: A role for nifedipine? Amer. J. Cardiol.44, 793–797 (1979).

    PubMed  Google Scholar 

  18. Heupler, Jr. F. A., W. L. Proudfit, M. Razavi, E. K. Shirey, R. Greenstreet, W. C. Sheldon: Ergonovine maleate provocative test for coronary arterial spasm. Amer. J. Cardiol.41, 631–640 (1978).

    PubMed  Google Scholar 

  19. Innes, I. R.: Identification of the smooth muscle excitatory receptors for ergot alkaloids. Brit. J. Pharmacol.19, 120–128 (1962).

    Google Scholar 

  20. Kelley, K. O., E. O. Feigl: Segmental α-receptor-mediated vasoconstriction in the canine coronary circulation. Circulat. Res.43, 908–917 (1978).

    PubMed  Google Scholar 

  21. Kruszynski, M., B. Lammek, M. Manning, J. Seto, J. Haldar, W. H. Sawyer: [1-(β-Mercapto-β,β-cyclopentamethylenepropionic acid), 2-(o-methyl) tyrosine] arginine-vasopressin and [1-(β-Mercapto-β,β-cyclopentamethylenepropionic acid)] arginine-vasopressin, two highly potent antagonists of the vasopressor response to arginine-vasopressin. J. Med. Chem.23, 364–368 (1980).

    PubMed  Google Scholar 

  22. Malayan, S. A., D. J. Ramsay, L. C. Keil, I. A. Reid: Effects of increase in plasma vasopressin concentration on plasma renin activity, blood pressure, heart rate, and plasma corticosteroid concentration in conscious dogs. Endocrinology107, 1899–1904 (1980).

    PubMed  Google Scholar 

  23. Maseri, A., S. Chierchia, A. L'Abbate: Pathogenetic mechanisms underlying the clinical events associated with atherosclerotic heart disease. Circulation62, V3-V13 (1980).

    PubMed  Google Scholar 

  24. Mudge, Jr. G. H., W. Grossman, R. M. Mills, Jr., M. Lesch, E. Braunwald: Reflex increase in coronary vascular resistance in patients with ischemic heart disease. New Engl. J. Med.295, 1333–1337 (1976).

    PubMed  Google Scholar 

  25. Müller-Schweinitzer, E.: The mechanism of ergometrine-induced coronary arterial spasm: In vitro studies on canine arteries. J. Cardiovasc. Pharmacol.2, 645–655 (1980).

    PubMed  Google Scholar 

  26. Orlick, A. E., D. R. Ricci, P. R. Cipriano, D. F. Guthaner, D. C. Harrison: Coronary hemodynamic effects of ergonovine maleate in human subjects. Amer. J. Cardiol.45, 48–52 (1980).

    PubMed  Google Scholar 

  27. Pagani, M., H. Baig, A. Sherman, W. T. Manders, P. Quinn, T. Patrick, D. Franklin, S. F. Vatners: Measurement of multiple simultaneous small dimensions and study of arterial pressure-dimension relations in conscious animals. Amer. J. Physiol.235, H610–H617 (1978).

  28. Raizner, A. E., R. A. Chahine, T. Ishimori, M. S. Verani, N. Zacca, N. Jamal, R. R. Miller, R. J. Luchi: Provocation of coronary artery spasm by the cold pressor test. Circulation62, 925–932 (1980).

    PubMed  Google Scholar 

  29. Rankin, J. S., P. A. McHale, C. E. Arentzen, D. Ling, J. C. Greenfield, Jr., R. W. Anderson: The three-dimensional dynamic geometry of the left ventricle in the conscious dog. Circulat. Res.39, 304–313 (1976).

    PubMed  Google Scholar 

  30. Ricci, D. R., A. E. Orlick, P. R. Cipriano, D. F. Guthaner, D. C. Harrison: Altered adrenergic activity in coronary arterial spasm: insight into mechanism based on study of coronary hemodynamics and the electrocardiogram. Amer. J. Cardiol.43, 1073–1079 (1979).

    PubMed  Google Scholar 

  31. Rich, S., L. E. Ford, J. Al-Sadir: The angiographic effect of ergonovine and nifedipine in coronary artery spasm. Circulation62, 1127–1130 (1980).

    PubMed  Google Scholar 

  32. Rowe, J. W., R. L. Shelton, J. H. Helderman, R. E. Vestal, G. L. Robertson: Influence of the emetic reflex on vasopressin release in man. Kidney Int.16, 729–735 (1979).

    PubMed  Google Scholar 

  33. Saeed, M., O. Sommer, J. Holtz, E. Bassenge: α-Adrenoceptor blockade by phentolamine causes β-adrenergic vasodilation by increased catecholamine release due to presynaptic α-blockade. J. Cardiovasc. Pharmacol. (in press).

  34. Schroeder, J. S., J. L. Bolden, R. A. Quint, P. A. Clark, W. G. Hayden, C. B. Higgins, L. Wexler: Provocation of coronary spasm with ergonovine maleate. Amer. J. Cardiol.40, 487–491 (1977).

    PubMed  Google Scholar 

  35. Stein, I.: Observations on the action of ergonovine on the coronary circulation and its use in the diagnosis of coronary artery insufficiency. Amer. Heart J.37, 36–45 (1949).

    Google Scholar 

  36. Tomoike, H., H. Ootsubo, K. Sakai, Y. Kikuchi, M. Nakamura: Continuous measurements of coronary artery diameter in situ. Amer. J. Physiol.240, H73–H79 (1981).

    Google Scholar 

  37. Vatner, S. F., M. Pagani, W. T. Manders, A. D. Pasipoularides: Alpha-adrenergic vasoconstriction and nitroglycerin vasodilation of large coronary arteries in the conscious dog. J. Clin. Invest.65, 5–14 (1980).

    PubMed  Google Scholar 

  38. Waters, D. D., P. Theroux, J. Szlachicic, F. Dauwe, J. Crittin, R. Bonan, H. F. Mizgala: Ergonovine testing in a coronary care unit. Amer. J. Cardiol.46, 922–930 (1980).

    PubMed  Google Scholar 

  39. Yasue, H., M. Touyama, M. Shimamoto, H. Kato, S. Tanaka, F. Akiyama: Role of autonomic nervous system in the pathogenesis of Prinzmetal's variant form of angina. Circulation50, 534–539 (1974).

    PubMed  Google Scholar 

Download references

Author information

Author notes

  1. J. Holtz, W. Held, O. Sommer, G. Kühne & E. Bassenge

    Present address: Lehrstuhl für Angewandte Physiologie der Universität Freiburg i. Br., Hermann-Herder-Straße 7, D-7800, Freiburg

Authors and Affiliations

    Authors
    1. J. Holtz
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. W. Held
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. O. Sommer
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. G. Kühne
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. E. Bassenge
      View author publications

      You can also search for this author in PubMed Google Scholar

    Additional information

    Supported by Deutsche Forschungsgemeinschaft. Dedicated to Prof. Dr. A. Fleckenstein on the occasion of his 65th birthday.

    Rights and permissions

    Reprints and permissions

    About this article

    Cite this article

    Holtz, J., Held, W., Sommer, O. et al. Ergonovine-induced constrictions of epicardial coronary arteries in conscious dogs: α-adrenoceptors are not involved. Basic Res Cardiol 77, 278–291 (1982). https://doi.org/10.1007/BF01908043

    Download citation

    • Received:

    • Issue Date:

    • DOI: https://doi.org/10.1007/BF01908043

    Key words

    Search

    Navigation