Cardiovascular Pharmacology
Alkharfy, K, Gao, Y, Leung, S, Xu, A, Vanhoutte, P, Detremmerie, CMS · Basic & Clinical Pharmacology & Toxicology · 2014
Background:The A 1, P2Y 1 and P2Y 6 receptors are expressed in cardiac tissue and activated by purines (ATPadenosine triphosphate), which are released by sympathetic neurons, endothelial cells and other tissues such as cardiomyocytes.The ATP modulates the cardiac inotropism and chronotropism.Therefore, this study aimed to investigate the role of purinergic receptors on cardiac arrest induced by ATP and its signaling pathway in isolated right atria (RA) of Wistar rats (WR).Methods: RA from WR (4-6 months) were isolated and mounted in isolated organ bath.The RA presented spontaneous beatings and frequency between 180 and 460 bpm was considered an inclusion criterion.We studied the effect of ATP (0.001 mM to 1 mM) on frequency of RA in the absence or presence of DPCPX-a selective antagonist of the adenosine A 1 receptor (1-100 nM/pre-incubated for 40 min), MRS 2179a selective antagonist of P2Y 1 receptor (1-100 nM/pre-incubated for 30 min) and MRS 2578a selective antagonist of P2Y 6 receptor (1-100 nM/pre-incubated for 30 min).The results were analyzed by unpaired t test and one-way ANOVA.All experiments procedures were approved by the Ethics Committee of UNIFESP (n° 0778/11).Results: ATP (1 mM to 30 lM) produced an initial negative chronotropic effect (NCE) which lasted 60-90 s and a negative inotropic effect (NIE).After that, the chronotropism gradually increased, showing a positive chronotropic effect (PCE) that lasted 400 s and a positive inotropic effect (PIE).ATP at 300 lM induced only a NCE.At 1 mM ATP abolished the atrial contraction.DPCPX (30 nM) and MRS 2179 (100 nM) prevented the cardiac arrest produced by ATP (1 mM) in Wistar rats.However, MRS 2578 was unable to inhibit this effect.Conclusion: The results suggest that the cardiac arrest induced by ATP was due to the activation of A 1 and P2Y 1 receptors from Wistar rats.