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

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

Author Camara, Henrique Autor UNIFESP Google Scholar
da Silva Junior, Edilson Dantas Autor UNIFESP Google Scholar
Garcia, Antonio G. Google Scholar
Jurkiewicz, Aron Autor UNIFESP Google Scholar
Dantas Rodrigues, Juliano Quintella Autor UNIFESP Google Scholar
Abstract 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 A(1) adenosine receptor agonist CPA (0.1-1 mu M), and muscarinic receptor agonists, carbachol (0.3-1 mu M) and acetylcholine (1 mM). After establishing the cardiac arrest, the A1 adenosine receptor antagonist DPCPX (0.3-30 mu M), the muscarinic receptor antagonist atropine (10 nM to 100 mu M) or the phosphodiesterase inhibitor IBMX (10-300 mu M) 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.
Keywords Cardiac arrest
Sinoatrial node
Adenosine receptor
Muscarinic receptor
DPCPX
xmlui.dri2xhtml.METS-1.0.item-coverage Amsterdam
Language English
Sponsor FAPESP
Capes
Grant number FAPESP: 13/20402-6
Capes: PNPD - 1864/2008
Date 2018
Published in European Journal Of Pharmacology. Amsterdam, v. 819, p. 42248, 2018.
ISSN 0014-2999 (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Bv
Extent set/15
Origin http://dx.doi.org/10.1016/j.ejphar.2017.09.030
Access rights Closed access
Type Article
Web of Science ID WOS:000419629200002
URI https://repositorio.unifesp.br/handle/11600/54263

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