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Sex‐specific Infarct Resistance is Abolished by Pre‐Ischemic Administration of Chelerythrine
Author(s) -
Edwards Andy Garreth,
Chicco Adam J,
Zachman Derek K,
Lynch Joshua M,
Moore Russell L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.71
Subject(s) - chelerythrine , blockade , medicine , protein kinase c , ischemia , antagonist , endocrinology , washout , pharmacology , cardiology , kinase , chemistry , receptor , biochemistry
The female myocardium, relative to that of the male, is resistant to ischemic tissue injury, particularly when post‐ischemic infarct size is taken as the end‐point measure of that injury. This infarct resistance is dependent upon function of the sarcolemmal K ATP (sarcK ATP ) channel. Here we investigate a role for Protein Kinase C (PKC, a likely regulator of sarcK ATP ) in the effector pathway of sex‐specific infarct resistance. Hearts from male (M) and female (F) Sprague‐Dawley rats were excised and Langendorff perfused for 30‐minutes prior to a 1h/2h ischemia/reperfusion challenge. During the 20 minutes directly preceding I/R, an isoform non‐specific PKC antagonist (2 μM Chelerythrine, Chel ) was administered to subsets of male (MC), and female (FC) rats. Ischemia then proceeded without washout. A significant (P < 0.05) ‘drug x sex’ interaction was observed in the absence of main effects for sex and drug ( Chel treatment). Subsequent pair‐wise comparisons indicated significant sex‐specific infarct resistance among the untreated females (M = 35.97 ± 4.33%, F = 20.89 ± 2.31%), and the complete abrogation of that resistance by PKC blockade (FC = 32.43 ± 3.72%), without any effect of Chel on infarct size among males (MC = 34.65 ± 3.54%, M vs. MC: P > 0.5). From these data we conclude that pre‐ischemic PKC blockade by Chelerythrine abolishes the sex‐specific infarct resistance characteristic of the female rat myocardium.