In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 110, No. 19 ( 2004-11-09), p. 3100-3107
Abstract:
Background— Whereas in the past, androgens were mainly believed to exert adverse effects on the cardiovascular system, recent experimental data postulate a benefit of testosterone for recovery of myocardial function after ischemia/reperfusion injury. Thus, we examined whether testosterone might improve myocardial tolerance to ischemia due to activation of mitochondrial (mitoK ATP ) and/or sarcoplasmatic (sarcK ATP ) K ATP channels. Methods and Results— In a cellular model of ischemia, testosterone significantly decreased the rate of ischemia-induced death of cardiomyocytes that could be prevented by 5-hydroxydecainoic acid but was unaffected by the sarcK ATP blocker HMR1098 and the testosterone receptor antagonist flutamide. To index mitoK ATP , mitochondrial flavoprotein fluorescence was measured. Testosterone induced a highly significant increase in mitochondrial flavoprotein fluorescence in intact myocytes and isolated mitoplasts that could be abolished by 5-hydroxydecainoic acid. Testosterone-mediated flavoprotein oxidation of mitoplasts was K + dependent and ATP sensitive. In mitoplast-attached single-channel recordings, testosterone directly activated an ATP-sensitive K + channel of the inner mitochondrial membrane. Addition of the K ATP channel opener diazoxide and pinacidil to the cytosolic solution activated the ATP-sensitive K + current comparable to testosterone, whereas 5-hydroxydecainoic acid and glibenclamide inhibited the testosterone-induced current. Patch-clamp experiments of intact myocytes in whole-cell configuration did not demonstrate any effect of testosterone on sarcK ATP channels. Conclusions— Our results provide direct evidence for the existence of cardiac mitoK ATP and a link between testosterone-induced cytoprotection and activation of mitoK ATP . Endogenous testosterone might play a more important role in recovery after myocardial infarction than is currently assumed.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.0000146900.84943.E0
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2004
detail.hit.zdb_id:
1466401-X
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