Summary
A single subcutaneous dose (1 mg/kg) of isoproterenol (ISO) increases the net calcium-45 uptake into the ventricular myocardium of normal rats by a factor of 4 within 6 hours. When the same dose of ISO was administered to rats with aortic constriction the rise in labelled Ca uptake by the hypertrophied myocardium of the left ventricle was greatly reduced. A decrease in ISO-induced Ca uptake also occurred in the non-hypertrophied right ventricular myocardium. Consequently, the stimulatory effect of ISO on the Ca-dependent high energy phosphate consumption was considerably diminished. A similar restriction of ISO-induced radiocalcium uptake and ATP utilization occurred in hypertrophied hearts of chronically ISO-treated rats or when the rats were exposed to other forms of experimental stress such as bleeding or cold. Although the ISO-induced cardiomegaly was reversed within 7 days, the insensitivity to β-adrenergic stimulation persisted for more than 3 weeks. The results indicate that the decrease in responsiveness to β-adrenergic agents is not due to the hypertrophy itself but must be considered to be an independent phenomenon — possibly resulting from adaptation to chronic β-adrenergic overstimulation.
Dedicated to Prof. Dr. A. Fleckenstein on the occasion of his 60th birthday.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Balazs, T.: Cardiotoxicity of isoproterenol in experimental animals. Influence of stress, obesity, and repeated dosing. In: Recent Advances in Studies on Cardiac Structure and Metabolism, Vol. 1, p. 770–778. Myocardiology, ( E. Bajusz and G. Rona, eds.) (Baltimore 1972 ).
Fleckenstein, A.: Specific inhibitors and promoters of calcium action in the excitation-contraction coupling of heart muscle and their role in the prevention or production of myocardial lesions. In: Calcium and the Heart, p. 135–188 ( P. Harris and L. Opie, eds. ), ( London-New York 1971 ).
Fleckenstein, A., J. Janke, H. J. Döring, O. Leder: Key role of Ca in the production of noncoronarogenic myocardial necroses. In: Recent Advances in Studies on Cardiac Structure and Metabolism, Vol. 6, p. 21–32. Pathophysiology and Morphology of Myocardial Cell Alterations (A. Fleckenstein and G. Rona, eds.), ( Baltimore 1975 ).
Hein, B., O. Pachinger, J. Janke, A. Fleckenstein: Changes in isoproterenolinduced transmembrane Ca uptake and high-energy phosphate content of the hypertrophied ventricular myocardium of rats. In: Les Surcharges Cardiaques, Collogue INSERM, p. 205–208. ( P. Y. Hatt, ed.) (Paris 1972 ).
Hein, B., A. Fleckenstein, J. Janke, K. Eckardt, H. J. Ludin: Einschränkung der Isoproterenol-induzierten 45Ca“-Netto-Aufnahme and der Utilisation von energiereichem Phosphat im hypertrophierten Rattenmyokard. Verh. Dtsch. Ges. Kreislaufforschg. 38, 196 (1972).
Hein, B., R. Hein, H. Sigel, J. Janke: Einschränkung ß-adrenerger Myokardreaktionen (95Ca-Aufnahme, ATP-Utilisation) bei Isoproterenol-induzierter Cardiomegalie. Verh. Dtsch. Ges. Kreislaufforschg. 39, 161 (1973).
Hein, B., R. Hein, J. Janke: Restriction of ß-adrenergic responsiveness in hypertrophied hearts of chronically isoproterenol-treated rats. In: Recent Advances in Studies on Cardiac Structure and Metabolism, Vol. 7, p. 359–367. Biochemistry and Pharmacology of Myocardial Hypertrophy, Hypoxia, and Infarction, (P. Harris, R. J. Bing, A. Fleckenstein, eds.), ( Baltimore 1976 ).
Irmer, M., G. Köhler, H. Friedrichs, E. Eschenbruch, H. J. Döring: Attenuation of ß-adrenergic cardiac responses in chronically hypoxic rats with right ventricular hypertrophy. In: Recent Advances in Studies on Cardiac Structure and Metabolism, Vol. 7, p. 351–358. Biochemistry and Pharmacology of Myocardial Hypertrophy, Hypoxia, and Infarction, (P. Harris, R. J. Bing, A. Flekkenstein, eds.), ( Baltimore 1976 ).
Janke, J., A. Fleckenstein, W. Jaedicke: Inhibition of the isoproterenolinduced radiocalcium uptake into the ventricular myocardium by Ca-antagonistic inhibitors of excitation-contraction coupling (Isoptin = verapamil, iproveratril or compound D 600). Pflügers Arch. ges. Physiol. 316, R 10 (1970).
Reuter, H.: Über die Wirkung von Adrenalin auf den cellulären Ca-Umsatz des Meerschweinchenvorhofs. Naunyn-Schmiedebergs Arch. Exp. Pathol. Pharmakol. 251, 401 (1965).
Rona, G., J. Dusek, I. Huttner, D. Kahn: Studies on myocardial resistance. In: Proceedings II Annual Meeting of the International Study Group for Research in Cardiac Metabolism, p. 173–204, Istituto Lombardo, Fondazione Baselli (Gargnano, Italy 1970 ).
Selye, H., R. Veilleux, S. Grasso: Protection by coronary ligation against isoproterenol-induced myocardial necrosis. Proc. Soc. Exp. Biol. Med. 104, 343 (1960).
Spann, J. F., C. A. Chidsey, P. E. Pool, E. Braunwald: Mechanism of nor-epinephrine depletion in experimental heart failure produced by aortic constriction in the guinea pig. Circulat. Res. 17, 312 (1965).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1977 Dr. Dietrich Steinkopff Verlag, Darmstadt
About this paper
Cite this paper
Hein, B., Janke, J. (1977). Restriction of β-adrenergic responsiveness in hypertrophied ventricular myocardium of rats. In: Jacob, R. (eds) The Hypertrophied Heart. Steinkopff. https://doi.org/10.1007/978-3-642-85299-2_30
Download citation
DOI: https://doi.org/10.1007/978-3-642-85299-2_30
Publisher Name: Steinkopff
Print ISBN: 978-3-7985-0482-0
Online ISBN: 978-3-642-85299-2
eBook Packages: Springer Book Archive