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

Burley, Dwaine Simon and Baxter, Gary Francis ORCID: https://orcid.org/0000-0002-7887-6841 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:	Schools > Pharmacy
Uncontrolled Keywords:	Ischaemia–reperfusion; Postconditioning; Natriuretic peptides
Publisher:	Elsevier
ISSN:	0022-2828
Last Modified:	17 Oct 2022 09:59
URI:	https://orca.cardiff.ac.uk/id/eprint/6457

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