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Cardiac alpha- and beta-adrenergic receptor alterations in diabetic cardiomyopathy

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Summary

The effect of chronic experimental diabetes on the adrenergic receptors in the rat heart was investigated. Diabetes was induced by streptozotocin (65 mg/kg; i.v.) administration, animals were sacrificed 8 weeks later, and positive as well as negative dF/dt values were determined in isolated papillary muscle preparations. Stimulation of the contractile force generation by isoproterenol and methoxamine was attenuated in diabetic preparations. Beta-and alpha-adrenergic receptor bindings were determined in cardiac membranes by employing3H-dihydroalprenolol and3H-dihydroergocryptine respectively. Reduced number of beta- and alpha-receptor binding sites without changes in the affinity constants were observed in diabetic myocardium. Such a decrease in alpha- and beta-receptor density in the heart may account for the depressed contractile responsiveness to adrenergic stimuli in diabetic cardiomyopathy.

Zusammenfassung

Es wurde der Einfluß eines chronischen, experimentellen Diabetes auf die adrenergen Rezeptoren des Rattenherzens untersucht. Diabetes wurde durch Streptozotocin (65 mg/kg i.v.) erzeugt. Die Untersuchungen wurden 8 Wochen nach Verabreichung durchgeführt. Es wurden positive und negative dF/dt-Werte (Geschwindigkeit der Kraftentwicklung) von isolierten Papillarmuskeln bestimmt. Die durch Isoproterenol und Methoxamin gesteigerte Kraftentwicklung war bei Ratten mit Diabetes vermindert. Die Bindungseigenschaften von Beta-und Alpha-rezeptoren in den Membranen des Herzens wurden mit Hilfe von3H-dihydroalprenolol und3H-dihydroergocryptin bestimmt. Im diabetischen Myokard war die Zahl der Beta- und Alpharezeptor-Bindungsstellen vermindert, nicht jedoch die Affinitätskonstanten. Die verringerte Beta- und Alpharezeptoren-Dichte im Herz könnte für die verminderte Ansprechbarkeit der Mechanik auf adrenerge Reize bei der diabetischen Kardiomyopathie verantwortlich sein.

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Author notes

  1. N. S. Dhalla (Professor of Physiology)

    Present address: Experimental Cardiology Section, Department of Physiology, Faculty of Medicine, University of Manitoba, R3E OW3, Winnipeg, Manitoba, Canada

Authors and Affiliations

  1. Experimental Cardiology Section, Department of Physiology, Faculty of Medicine, University of Manitoba, R3E OW3, Winnipeg, Manitoba, Canada

    C. E. Heyliger, G. N. Pierce, P. K. Singal & R. E. Beamish

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  1. C. E. Heyliger
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  2. G. N. Pierce
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  3. P. K. Singal
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  4. R. E. Beamish
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  5. N. S. Dhalla
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Heyliger, C.E., Pierce, G.N., Singal, P.K. et al. Cardiac alpha- and beta-adrenergic receptor alterations in diabetic cardiomyopathy. Basic Res Cardiol 77, 610–618 (1982). https://doi.org/10.1007/BF01908314

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  • DOI: https://doi.org/10.1007/BF01908314

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