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  • Title: Role of KATP channel in heat shock and pharmacological preconditioning.
    Author: Kukreja RC.
    Journal: Ann N Y Acad Sci; 1999 Jun 30; 874():211-21. PubMed ID: 10415533.
    Abstract:
    Heat shock (HS) and 4-monophosphoryl lipid A (MLA, a non-toxic analogue of endotoxin) protects the myocardium against ischemia-reperfusion injury. We studied the involvement of ATP-sensitive potassium channel (KATP channel) in ischemic protection induced by these stimuli. Anesthetized rabbits were preconditioned with either HS (by raising temperature to 42 degrees C for 15 min) or intravenous pretreatment with MLA (35 micrograms/kg). After 24 h, animals were re-anesthetized and subjected to 30-min regional ischemia followed by 180-min reperfusion (I/R). KATP channel blockers glibenclamide and/or 5-hydroxydecanoate (5-HD) were used to inhibit channel function. The 72 kD heat shock protein (HSP-72) was measured by Western blots. HS produced a marked reduction in infarct size (39.4 +/- 8.1% to 14.3 +/- 2.5%, p < 0.05) that was abolished by glibenclamide (42.3 +/- 3.2%) and 5-HD (33.7 +/- 4.8%) when given before I/R. These drugs failed to block HS protection when given before HS. Expression of HSP-72 was increased in all HS groups as compared to non-HS groups in both glibenclamide and 5-HD-treated rabbits. Similarly, pretreatment with MLA reduced infarct size from 40 +/- 8.6% to 15.1 +/- 1.5% (p < 0.05). The infarct size increased to 51.9 +/- 5.8 with 5-HD in MLA-treated rabbits. 5-HD did not alter infarct size significantly when given in vehicle-treated control rabbits. These data suggest that HS and MLA exert their anti-ischemic effect through activation of KATP channel.
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