α-Adrenergic Regulation of Myocardial Performance in the Exercising Dog: Evidence for Both Presynaptic α1- and α2-Adrenoceptors

  • Brian D. Guth
  • E. Thaulow
  • G. Heusch
  • R. Seitelberger
  • J. RossJr.
Conference paper

Summary

New evidence supporting both presynaptic α1- and α2-adrenoceptors playing a role in the regulation of myocardial contractile performance in the exercising dog is reviewed. Studies utilized chronically instrumented dogs having sonomicrometers for the measurement of regional wall thickening and transducers for the measurement of left ventricular and systemic hemodynamics. During steady state exercise, either the selective α1-adrenoceptor blocker prazosin (80μg/kg) or the selective α2-adrenoceptor blocker idazoxan (80μg/kg) was infused into the left atrium while exercise continued. Immediately following the administration of either α-adrenoceptor blocking agent, there were substantial increases in heart rate, left ventricular dP/dt and regional contractile function as assessed using sonomicrometers, and norepinephrine release by the myocardium increased substantially. β-adrenergic blockade prevented the heart rate and contractile effects of either α1 - or α2-adrenoceptor blocker whereas norepinephrine release was further enhanced. These effects could not be attributed to baroreceptor unloading. In dogs studied under resting conditions with norepinephrine infusion to produce an increase in dP/dt similar to that observed during treadmill exercise, no sympathetic augmentation was observed following either α-blocker. Together, these studies provide evidence that both α1- and α2-adrenoceptors participate in the modulation of sympathetic neuronal norepinephrine release in the canine myocardium.

Keywords

Catheter Norepinephrine Hull Choline Catecholamine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Andersson R, Holmberg S, Svedmyr N, Aberg G (1972) Adrenergic alpha-and beta-receptors in coronary vessels in man. Acta Med Scand 191, 241–244PubMedGoogle Scholar
  2. 2.
    Chen DG, Dai X-Z, Zimmerman BG, Bache RJ (1988) Postsynaptic α1-and α2-adrenergic mechanisms in coronary vasoconstriction. J Cardiovasc Pharmacol 11, 61–67PubMedCrossRefGoogle Scholar
  3. 3.
    Guth BD, Thaulow E, Heusch G, Seitelberger R, Ross J Jr (1990) Myocardial effects of selective alpha-adrenoceptor blockade during exercise in dogs. Circ Res 66, 1703–1712PubMedCrossRefGoogle Scholar
  4. 4.
    Gwirtz PA, Overn SP, Mass HJ, Jones CE (1986) Alpha 1-adrenergic constriction limits coronary flow and cardiac function in running dogs. Am J Physiol 250:H1117–H1126PubMedGoogle Scholar
  5. 5.
    Heusch G, Deussen A, Schipke J, Thämer V (1984) α1-and α2-adrenoceptor-mediated vasoconstriction of large and small canine coronary arteries in vivo. J Cardiovasc Pharmacol 6, 961–968PubMedCrossRefGoogle Scholar
  6. 6.
    Heyndrickx GR, Vilaine JP, Moerman EJ, Leusen I (1984) Role of prejunctional alpha 2-adrenergic receptors in the regulation of myocardial performance during exercise in conscious dogs. Circ Res 54, 683–693PubMedCrossRefGoogle Scholar
  7. 7.
    Holtz J, Mayer E, Bassenge E (1977) Demonstration of alpha-adrenergic coronary control in different layers of canine myocardium by regional myocardial sympathectomy. Pfluegers Arch 372, 187–194CrossRefGoogle Scholar
  8. 8.
    Holtz J, Saeed M, Sommer O, Bassenge E (1982) Norepinephrine constricts the canine coronary bed via postsynaptic α2-adrenoceptors. Eur J Pharmacol 82, 199–202PubMedCrossRefGoogle Scholar
  9. 9.
    Homcy CJ, Graham RM (1985) Molecular characterization of adrenergic receptors. Circ Res 56, 635–650PubMedCrossRefGoogle Scholar
  10. 10.
    McCall RB, Humphrey SJ (1981) Evidence for a central depressor action of postsynaptic alpha-1-adrenergic receptor antagonists. J Auton Nerv System 3, 9–23CrossRefGoogle Scholar
  11. 11.
    McGrath JC, Brown CM, Wilson VG (1983) Alpha-receptors: a critical review. Med Res Rev 9, 407–533CrossRefGoogle Scholar
  12. 12.
    McGrattan PA, Brown JH, Brown OM (1987) Parasympathetic effects on in vivo rat heart can be regulated through an alpha-1-adrenergic receptor. Circ Res 60, 465–471PubMedCrossRefGoogle Scholar
  13. 13.
    Mohrman DE, Feigl EO (1978) Competition between sympathetic vasoconstriction and metabolic vasodilation in the canine coronary circulation. Circ Res 42, 79–86PubMedCrossRefGoogle Scholar
  14. 14.
    Schulz R, Heusch G, Oudiz R, Guth BD (1989) Coronary pressure and flow have no independent effect on contractility in anesthetized swine. Faseb J 3:A405Google Scholar
  15. 15.
    Schulz R, Hücking G, Heusch G (1989) “CORDAT” — a new data acquisition and reduction program. Eur Heart J 10:309(abstr.)Google Scholar
  16. 16.
    Starke K (1987) Presynaptic alpha-autoreceptors. Rev Physiol Biochem Pharmacol 107, 73–146PubMedCrossRefGoogle Scholar
  17. 17.
    Starke K, Göthert M, Kilbinger H (1989) Modulation of neurotransmitter release by presynaptic autoreceptors. Physiol Rev 69, 864–989PubMedGoogle Scholar
  18. 18.
    Strader JR, Gwirtz PA, Jones CE (1988) Comparative effects of α1-and α2-adrenoceptors in modulation of coronary flow during exercise. J Pharmacol Exp Ther 246, 772–778PubMedGoogle Scholar
  19. 19.
    Wetzel GT, Brown JH (1985) Presynaptic modulation of acetylcholine release from cardiac parasympathetic neurons. Am J Physiol 248:H33–H39PubMedGoogle Scholar
  20. 20.
    Young MA, Vatner DE, Knight DR, Graham RM, Homcy CJ, Vatner SF (1988) α-adrenergic vasoconstriction and receptor subtypes in large coronary arteries of calves. Am J Physiol 255:H1452–H1459PubMedGoogle Scholar
  21. 21.
    Zuberbuhler RC, Bohr DF (1965) Responses of coronary smooth muscle to catecholamines. Circ Res 16, 431–440PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • Brian D. Guth
    • 1
  • E. Thaulow
    • 1
  • G. Heusch
    • 1
  • R. Seitelberger
    • 1
  • J. RossJr.
    • 1
  1. 1.Seaweed Canyon Laboratory, Department of MedicineUniversity of CaliforniaLa JollaUSA

Personalised recommendations