Role of A1 adenosine receptor in the regulation of coronary flow

Huda E. Tawfik, Bunyen Teng, R. Ray Morrison, J. Schnermann, S. Jamal Mustafa

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

To determine whether A1 adenosine receptors (AR) participate in adenosine-induced changes of coronary flow, isolated hearts from A 1AR-/- and A1AR+/+ mice were perfused under constant pressure, and the effects of nonselective and selective agonists were examined. Adenosine, 5′-N-ethylcarboxamidoadenosine (NECA, nonselective), and the selective A2AAR agonist 2-2- carboxyethylphenethylamino-5′-N-ethylcarboxamidoadenosine (CGS-21680) augmented maximal coronary vasodilation in A1AR-/- hearts compared with A1AR+/+ hearts. Basal coronary flow was increased (P < 0.05) in A1AR-/- hearts compared with A1AR+/+ hearts: 2.548 ± 0.1 vs. 2.059 ± 0.17 ml/min. In addition, selective activation of A1AR with 2-chloro-N6-cyclopentyladenosine (CCPA) at nanomolar concentrations (1-100 nM) did not significantly change coronary flow; at higher concentrations, CCPA increased coronary flow in A1AR-/- and A 1AR+/+ hearts. Because deletion of A1AR increased basal coronary flow, it is speculated that this effect is due to removal of an inhibitory influence associated with A1AR. Adenosine and NECA at approximately EC50 (100 and 50 nM, respectively) increased coronary flow in A1AR+/+ hearts to 177.86 > 8.75 and 172.72 ± 17% of baseline, respectively. In the presence of the selective A1AR antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 50 nM), the adenosine- and NECA-induced increase in coronary flow in A 1AR+/+ hearts was significantly augmented to 216.106 ± 8.35 and 201.61 ± 21.89% of normalized baseline values, respectively. The adenosine- and NECA-induced increase in coronary flow in A1AR-/- hearts was not altered by DPCPX. These data indicate that A1AR may inhibit or negatively modulate coronary flow mediated by other AR subtypes (A2A and A2B).

Original languageEnglish (US)
Pages (from-to)H467-H472
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number1
DOIs
StatePublished - Jul 12 2006

Keywords

  • A adenosine receptor knockout
  • Adenosine receptor agonists
  • Adenosine receptor antagonists
  • Isolated mouse heart

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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