Approximation of A1 adenosine receptor reserve appertaining to the direct negative inotropic effect of adenosine in hyperthyroid guinea pig left atria

Krisztian Pak, Csaba Papp, Zoltan Galajda, Tamas Szerafin, Balazs Varga, Bela Juhasz, David Haines, Andras Jozsef Szentmiklosi, Arpad Tosaki, Rudolf Gesztelyi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Hyperthyroidism elevates cardiovascular mortality by several mechanisms, including increased risk of ischemic heart disease. Therefore, therapeutic strategies, which enhance tolerance of heart to ischemia-reperfusion injury, may be particularly useful for hyperthyroid patients. One promising cardioprotective approach is use of agents that cause (directly or indirectly) A1 adenosine receptor (A1 receptor) activation, since A1 adenosinergic pathways initiate protective mechanisms such as ischemic preconditioning. However, previously we found great A1 receptor reserve for the direct negative inotropic effect of adenosine in isolated guinea pig atria. This phenomenon suggests that weakening of atria is a possible side effect of A1 adenosinergic stimulant agents. Thus, the goal of the present investigation was to explore this receptor reserve in hyperthyroidism. Our recently developed method was used that prevents the rapid intracellular elimination of adenosine, allowing sufficient time for exogenous adenosine administered for the generation of concentration-response curves to exert its effect. Our method also allowed correction for the bias caused by the consequent endogenous adenosine accumulation. Our results demonstrate that thyroxine treatment does not substantially affect the A1 receptor reserve for the direct negative inotropic effect of adenosine. Consequently, if an agent causing A1 receptor activation is administered for any indication, the most probable adverse effect affecting the heart may be a decrease of atrial contractility in both eu- and hyperthyroid conditions.

Original languageEnglish
Pages (from-to)177-188
Number of pages12
JournalGeneral physiology and biophysics
Volume33
Issue number2
DOIs
Publication statusPublished - 2014

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Keywords

  • A1 adenosine receptor
  • Atrium
  • Heart
  • Inotropy
  • Receptor reserve
  • Receptorial responsiveness method
  • Thyroid hormones

ASJC Scopus subject areas

  • Biophysics
  • Physiology

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