Journal article

Publication year: 2009

Pages: 901-908

Journal: British Journal of Pharmacology

Volume number: 156

Issue number: 6

ISSN: 0007-1188

eISSN: 1476-5381

Open access status: Green

DOI Link: https://doi.org/10.1111/j.1476-5381.2008.00053.x

Publisher: Wiley

Abstract: 

Ischaemic preconditioning (IPC) and ischaemic post-conditioning (IPoC) activate signal transduction pathways that are also involved in receptor de- and re-sensitization such as phosphatidylinositol (PI) 3-kinase. Therefore, IPC and IPoC may affect post-infarct receptor coupling.

Rat isolated hearts (Langendorff mode, constant flow) were exposed to 45 min flow arrest followed by 120 min reperfusion, including IPC or IPoC. Control hearts were perfused without a 45 min flow arrest. Left ventricular developed pressure (LVdevP) was determined. Thirty min after reperfusion, hearts were exposed to parathyroid hormone-related peptide (PTHrP) or isoprenaline for 10 min to monitor receptor responsiveness. Reperfusion injury was quantified by enzyme release.

IPC and IPoC significantly reduced enzyme release compared with ischaemia and reperfusion alone by 75% and 62% respectively. Wortmannin or chelerythrine inhibiting either PI 3-kinase or protein kinase C, respectively, attenuated protection. Application of PTHrP 30 min after reperfusion did not change LVdevP in hearts exposed to ischaemia (+1 +/- 11%), but IPoC restored the normal and non-ischaemic response to PTHrP characterized by a negative inotropism (-8.3 +/- 3.9% and -12.9 +/- 6.1%). IPC restored a small negative inotropic effect (-4.4 +/- 4.7%). Application of a PTHrP receptor antagonist during the 45 min flow arrest attenuated receptor desensitization (Delta LVdevP: -6.1 +/- 1.7%). Wortmannin but not chelerythrine attenuated the re-sensitizing effect of IPoC on post-ischaemic receptor coupling (Delta LVdevP: +6.2 +/- 10.5 and -15.0 +/- 7.7%). As observed with PTHrP receptors, IPoC restored beta-adrenoceptors (Delta LVdevP: +9.3 +/- 11.8% vs. 62.3 +/- 15.8%).

IPoC restores PTHrP receptor coupling in a PI 3-kinase-dependent way. A similar mechanism may allow beta-adrenoceptor re-sensitization.

Harvard Citation style: Schreckenberg, R., Maier, T. and Schlueter, K. (2009) Post-conditioning restores pre-ischaemic receptor coupling in rat isolated hearts, British Journal of Pharmacology, 156(6), pp. 901-908. https://doi.org/10.1111/j.1476-5381.2008.00053.x

APA Citation style: Schreckenberg, R., Maier, T., & Schlueter, K. (2009). Post-conditioning restores pre-ischaemic receptor coupling in rat isolated hearts. British Journal of Pharmacology. 156(6), 901-908. https://doi.org/10.1111/j.1476-5381.2008.00053.x