Evidence for a role for both the adenosine A1 and A3 receptors in protection of isolated human atrial muscle against simulated ischaemia

Autor: C. S. Carr, D R Knight, H Masamune, R J Hill, W R Tracey, Scott P. Kennedy, Derek M. Yellon
Rok vydání: 1997
Předmět:
Zdroj: Cardiovascular Research. 36:52-59
ISSN: 0008-6363
DOI: 10.1016/s0008-6363(97)00160-0
Popis: Objective: Adenosine receptor activation has been implicated in the mechanism of ischaemic preconditioning protection. Evidence suggests adenosine A1 receptor involvement, and possibly A3 receptor involvement in the rabbit. This study investigated the roles of these receptors in human preconditioning. Human A1- and A3-selective compounds were chosen based on K i values for inhibition of N 6-(4-amino-3-[125I]iodobenzyl)adenosine (125I-ABA) binding to stably expressed recombinant human A1 and A3 receptors. Cyclopentyladenosine (CPA), a 194-fold selective A1 agonist, and iodobenzylmethylcarboxamidoadenosine (IBMECA), a 10-fold selective A3 agonist were used alone and in combination with dipropylcyclopentylxanthine (DPCPX) a 62-fold selective A1 antagonist. Methods: Human atrial trabeculae were superfused with oxygenated Tyrode's solution. After stabilisation, muscles underwent one of 8 protocols ( n = 6 per group), followed by 90 min of simulated ischaemia and 120 min of reoxygenation. The experimental endpoint was recovery of contractile function, presented as percentage baseline function. Results: 5 nM CPA (52.2±3.1%), 30 nM IBMECA (49.7±3.8%) and preconditioning (55.3±2.5%) produced similar functional recoveries at 120 min of reoxygenation; significantly different to controls (27.7±1.0%; P
Databáze: OpenAIRE