Cardiac arrest induced by muscarinic or adenosine receptors agonists is reversed by DPCPX through double mechanism

In the right atrium (RA), adenosine and acetylcholine inhibit the pacemaker function of the sinoatrial node and induce cardiac arrest. Pre-incubation of receptor antagonists is known to inhibit the cardiac arrest induced by these agonists; however, the effect of antagonist administration after established cardiac arrest has not been described. Therefore, we assessed whether specific receptor antagonists could revert cardiac arrest induced by adenosine and muscarinic receptors activation. RA isolated from adults Wistar rats were mounted in an organ bath containing Krebs solution. Cardiac arrest was induced by adenosine or ATP (1 mM), the A1 adenosine receptor agonist CPA (0.1-1 µM), and muscarinic receptor agonists, carbachol (0.3-1 µM) and acetylcholine (1 mM). After establishing the cardiac arrest, the A1 adenosine receptor antagonist DPCPX (0.3-30 µM), the muscarinic receptor antagonist atropine (10 nM to 100 µM) or the phosphodiesterase inhibitor IBMX (10-300 µM) were incubated in order to check for the return of spontaneous contractions. DPCPX reversed the cardiac arrest induced by adenosine, ATP and CPA. In addition, atropine reversed the cardiac arrest induced by carbachol. Unexpectedly, DPCPX also reversed the cardiac arrest induced by carbachol. Similarly to DPCPX, the phosphodiesterase inhibitor IBMX reversed the cardiac arrest induced by adenosine, CPA and carbachol. The antagonism of adenosine and acetylcholine receptors activation, as well as phosphodiesterase inhibition, are able to revert cardiac arrest. DPCPX restore spontaneous contractions via the selective antagonism of A1 adenosine receptor and through a secondary mechanism likely related to phosphodiesterase inhibition.