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Felodipine prevents the poststenotic myocardial ischemia induced by alpha2-adrenergic coronary constriction

  • New Calcium Antagonists
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Summary

Alpha2-adrenoceptor-mediated coronary constriction contributes to the precipitation of myocardial ischemia during sympathetic activation. Felodipine is a novel dihydropyridine calcium-channel antagonist with vascular selectivity. In this study, the effect of felodipine on alpha2-adrenoceptor-mediated poststenotic coronary constriction was investigated. In ten open-chest dogs, the selective alpha2-adrenoceptor agonist BHT 933 (200 μg IC) was infused before and after production of a severe stenosis on the left circumflex coronary artery. BHT 933 increased calculated resistance of the intact left circumflex coronary artery from 1.16±0.30 (SD) to 2.00±0.70 mmHg*min*100 g/ml (p<0.05) without changing posterior systolic wall thickening (sonomicrometry) (14.2±2.8% vs. 14.1±2.7%). In the presence of a severe stenosis, BHT 933 increased poststenotic coronary resistance from 1.59±0.54 to 2.88±1.16 mmHg*min*100 g/ml (p<0.05) and decreased posterior systolic wall thickening from 11.9±2.7% to 8.2±3.1% (p<0.05). In contrast, after intravenous pretreatment with felodipine (4 μg/kg), intracoronary infusion of BHT 933 did not change coronary resistance (1.69±0.61 vs. 1.61±0.64 mmHg*min*100 g/ml) and posterior systolic wall thickening (12.1±3.0% vs. 12.6±2.9%).

In conclusion, felodipine prevents alpha2-adrenoceptor-mediated coronary constriction and ischemic regional myocardial dysfunction distal to a severe coronary stenosis.

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References

  1. Schulz R, Guth BD, Heusch G. Pharmacological mechanisms to attenuate sympathetically induced myocardial ischemia.Cardiovasc Drugs Ther 1989;3:43–56.

    PubMed  Google Scholar 

  2. Gould KL, Lipscomb K, Calvert C. Compensatory changes of the distal coronary vascular bed during progressive coronary constriction.Circulation 1975;51:1085–1094.

    PubMed  Google Scholar 

  3. Heusch G, Deussen A. The effects of cardiac sympathetic nerve stimulation on the perfusion of stenotic coronary arteries in the dog.Circ Res 1983;53:8–15.

    PubMed  Google Scholar 

  4. Seitelberger R, Guth BD, Heusch G, et al. Intracoronary α2-adrenergic receptor blockade attenuates ischemia in conscious dogs during exercise.Circ Res 1988;62:436–442.

    PubMed  Google Scholar 

  5. Mudge GH, Goldberg S, Gunther S, et al. Comparison of metabolic and vasoconstrictor stimuli on coronary vascular resistance in man.Circulation 1979;59:544–550.

    PubMed  Google Scholar 

  6. Berkenboom GM, Abramowicz M, Vandermoten P, et al. Role of alpha-adrenergic coronary tone in exercise-induced angina pectoris.Am J Cardiol 1986;57:195–198.

    PubMed  Google Scholar 

  7. Chen DG, Dai X-Z, Zimmerman BG, et al. Postsynaptic α1 and α2-adrenergic mechanisms in coronary vasoconstriction.J Cardiovasc Pharmacol 1988;11:61–67.

    PubMed  Google Scholar 

  8. Holtz J, Saeed M, Sommer O, et al. Norepinephrine constricts the canine coronary bed via postsynaptic α2-adrenoceptors.Eur J Pharmacol 1982;82:199–202.

    PubMed  Google Scholar 

  9. Deussen A, Heusch G, Thämer V. α2-adrenoceptor-meditiated coronary vasoconstriction persists after exhaustion of coronary dilator reserve}.Eur J Pharmacol 1985;115: 147–153.

    PubMed  Google Scholar 

  10. van Zwieten PA, van Meel JCA. Timmermans PBMWM. Functional interaction between calcium antagonists and the vasoconstriction induced by the stimulation of postsynaptic α2-adrenoceptors.Circ Res 1983;52(Suppl I):77–80.

    Google Scholar 

  11. Motulsky HJ, Snavely MD, Hughes RJ, et al. Interaction of verapamil and other calcium channel blockers with α1 and α2-adrenergegic receptors.Circ Res 1983;52:226–231.

    PubMed  Google Scholar 

  12. Heusch G, Deussen A. Nifedipine prevents sympathetic vasoconstriction distal to severe coronary stenoses.J Cardiovasc Pharmacol 1984;6:378–383.

    PubMed  Google Scholar 

  13. Ljung B. Vascular selectivity of felodipine.Drugs 1985; 29:46–58.

    PubMed  Google Scholar 

  14. Verdouw PD, Wolffenbuttel BHR, Scheffer MG, Cardiovascular actions of the calmodulin inhibitor felodipine.Naunyn Schmiedebergs Arch Pharmacol 1983;323:350–354.

    PubMed  Google Scholar 

  15. Sjöquist PO, Adler G, Duker G, et al. Effects of felodipine, a new dihydropyridine vasodilator, on regional myocardial blood flow during acute coronary occlusion in the pig.J Cardiovasc Pharmacol 1983;5:202–206.

    PubMed  Google Scholar 

  16. Sjöquist PO, Duker G, Almgren O. Coronary collateral blood flow in acute myocardial ischemia is not increased by dihydropyridine-induced coronary vasodilatation.J Cardiovasc Pharmacol 1985;7:630–636.

    PubMed  Google Scholar 

  17. Sheridan JV, Thomas P, Routledge PA, et al. Effects of felodipine on haemodynamics and exercise capacity in patients with angina pectoris.Br J Clin Pharmacol 1987;23:391–396.

    PubMed  Google Scholar 

  18. Metcalfe MJ, Chan-Wah Hak NS, Jennings K. The effects of treatment with felodipine as a single agent in coronary artery disease.Br Heart J 1989;61:258–261.

    PubMed  Google Scholar 

  19. Verdecchia P, Gatteschi C, Benemio G, et al. Increased exercise tolerance and reduced electrocardiographic ischaemia 3 and 12 hours after oral felodipine in effort angina.Eur Heart J 1989;10:70–76.

    PubMed  Google Scholar 

  20. Feigl EO, D'Alecy LG. Normal arterial blood pH, oxygen and carbon dioxide tensions in unanesthetized dogs.J Appl Physiol 1972;32:152–153.

    Google Scholar 

  21. Schipke J, Heusch G, Schultz R, et al. An easy and quick implantation procedure for the measurement of myocardial wall thickness using sonomicrometry.Basic Res Cardiol 1987;82:411–414.

    Google Scholar 

  22. Canty Jr JM. Coronary pressure-function and steady-state pressure-flow relations during autoregulation in the unanesthetized dog.Circ Res 1988;63:821–836.

    PubMed  Google Scholar 

  23. Theroux P, Ross Jr J, Franklin D, et al. Regional myocardial function in the conscious dog during acute coronary occlusion and responses to morphine, propranolol, nitroglycerin, and lidocaine.Circulation 1976;53:302–314.

    PubMed  Google Scholar 

  24. Osakada G, Hess OM, Gallagher KP, et al. End-systolic dimension-wall thickness relations during myocardial ischemia in conscious dogs. A new approach for defining regional function.Am J Cardiol 1983;51:1750–1758.

    PubMed  Google Scholar 

  25. Feigl EO. Coronary physiology.Physiol Rev 1983;63:1–205.

    PubMed  Google Scholar 

  26. Chilian WM, Eastham CL, Layne SM, et al. Small vessel phenomena in the coronary microcirculation: Phasic intramyocardial perfusion and coronary microvascular dynamics.Prog Cardiovasc Dis 1988;31:17–38.

    PubMed  Google Scholar 

  27. Schaper W, Flameng W, Wüsten B., et al. The distribution of coronary collateral flow in normal hearts and after chronic coronary occlusion.Adv Exp Med Biol 1973;39:151–160.

    PubMed  Google Scholar 

  28. Gallagher KP, Kumada T, Koziol JA, et al. Significance of regional wall thickening abnormalities relative to transmural myocardial perfusion in anesthetized dogs.Circulation 1980;62:1266–1274.

    PubMed  Google Scholar 

  29. Gallagher KP, Osakada G, Matsuzaki M, et al. Myocardial blood flow and function with critical coronary stenosis in exercising dogs.Am J Physiol 1982;243:H698-H707.

    PubMed  Google Scholar 

  30. Gallagher KP, Matsuzaki M, Koziol JA, et al. Regional myocardial perfusion and wall thickening during ischemia in conscious dogs.Am. J Physiol 1984;247:H727-H738.

    PubMed  Google Scholar 

  31. Malliani A, Schwartz PJ, Zanchetti A. A sympathetic reflex elicited by experimental coronary occlusion.Am J Physiol 1969;217:703–709.

    PubMed  Google Scholar 

  32. Brown AM. Excitation of afferent cardiac sympathetic nerve fibres during myocardial ichemia.Br J Physiol 1967;190:35–53.

    Google Scholar 

  33. Uchida Y, Murao S. Excitation of afferent cardiac sympathetic nerve fibers during coronary occlusion.Am J Physiol 1974;226:1094–1099.

    PubMed  Google Scholar 

  34. Kumada T, Karliner JS, Pouleur H, et al. Effects of coronary occlusion on early ventricular diastolic events in conscious dogs.Am J Physiol 1979;237:H542-H549.

    PubMed  Google Scholar 

  35. Sheridan DJ, Culling W. Acute haemodynamic effects of felodipine in patients with coronary artery disease.Drugs 1985;29:87–89.

    PubMed  Google Scholar 

  36. Timmis AD, Smyth P, Kenny JF, et al. Effects of vasodilator treatment with felodipine on haemodynamic response to treadmill exercise in congestive heart failure.Br Heart J 1984;52:314–320.

    PubMed  Google Scholar 

  37. Tweddel AC, Hutton I. Felodipine in ventricular dysfunction.Eur Heart J 1986;7:54–60.

    PubMed  Google Scholar 

  38. Ross Jr J. Afterload mismatch and preload reserve: A conceptual framework for the analysis of ventricular function.Prog Cardiovasc Dis 1976;18:255–264.

    PubMed  Google Scholar 

  39. Ross Jr J. Cardiac function and myocardial contractility: A perspective.J Am Coll Cardiol 1983;1:52–62.

    PubMed  Google Scholar 

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  1. Abteilung für Pathophysiologie, Universitätsklinikum Essen, Hufelandstr. 55, 4300, Essen 1, FRG

    Thomas Ehring &  Gerd Heusch

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  1. Thomas Ehring
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  2. Gerd Heusch
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Ehring, T., Heusch, G. Felodipine prevents the poststenotic myocardial ischemia induced by alpha2-adrenergic coronary constriction. Cardiovasc Drug Ther 4, 443–449 (1990). https://doi.org/10.1007/BF01857752

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