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Activation of particulate guanylate cyclase during early reperfusion limits infarct size in the rat isolated heart

Burley, Dwaine Simon and Baxter, Gary Francis 2007. Activation of particulate guanylate cyclase during early reperfusion limits infarct size in the rat isolated heart. Journal of Molecular and Cellular Cardiology 42 (6(S)) , S209. 10.1016/j.yjmcc.2007.03.633

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Abstract

The natriuretic peptides protect ischaemic myocardium by activating cGMP-generating particulate guanylate cyclases (pGC). B-type natriuretic peptide (BNP) limits myocardial infarct size but the protective effect of BNP specifically at reperfusion has not been demonstrated. Moreover, the relationship between pGC/cGMP signalling and the postconditioning (pcond) mechanism is not known. We hypothesised: 1. BNP administered at reperfusion limits infarct size; 2. Pcond involves endogenous pGC activation. Male rat hearts were Langendorff-perfused, and subjected to 35 min regional ischaemia and 120 min reperfusion. Pcond was induced by applying 6 10 s periods of global ischaemia at the onset of reperfusion. Hearts were randomised to 15 min treatments, commencing 5 min prior to reperfusion with BNP, the soluble GC activator SNAP, or the pGC blocker isatin. Infarct size was measured using triphenyltetrazolium staining. Series 1 (n = 5–17) Infarct size (% of risk ) Series 2 (n = 6–9) Infarct size (% of risk) Control 40.8 ± 3.7 Control 34.5 ± 4.9 Pcond 16.0 ± 2.7** Pcond 14.9 ± 3.6** BNP 10 nM 22.9 ± 4.1** Isatin 100 μM 34.5 ± 4.9 SNAP 10 μM 33.7 ± 6.4 Pcond + Isatin 35.1 ± 6.0 Full-size table Table options * View in workspace * Download as CSV **P < 0.01 vs. Control (1-way ANOVA). Mean ± SEM. These data support the hypothesis that pGC activation during early reperfusion limits infarct size and contributes to pcond protection.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Uncontrolled Keywords: Ischaemia–reperfusion; Postconditioning; Natriuretic peptides
Publisher: Elsevier
ISSN: 0022-2828
Last Modified: 04 Jun 2017 01:57
URI: http://orca-mwe.cf.ac.uk/id/eprint/6457

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