In vivo exposure to chronic hypoxia is considered to be a cause of myocardial dysfunction, thereby representing a deleterious condition, but repeated aeration episodes may exert some cardioprotection. We investigated the possible role of ATP-sensitive potassium channels in these mechanisms. First, rats (n = 8/group) were exposed for 14 days to either chronic hypoxia (CH; 10% O2) or chronic hypoxia with one episode/day of 1-hr normoxic aeration (CH+A), with normoxia (N) as the control. Second, isolated hearts were Langendorff perfused under hypoxia (10% O2, 30 min) and reoxygenated (94% O2, 30 min) with or without 3 μM glibenclamide (nonselective K+ ATP channel-blocker) or 100 μM diazoxide (selective mitochondrial K+ ATP channel-opener). Blood gasses, hemoglobin concentration, and plasma malondialdehyde were similar in CH and CH+A and in both different from normoxic (P <0.01), body weight gain and plasma nitrate/nitrite were higher in CH+A than CH (P <0.01), whereas apoptosis (number of TUNEL-positive nuclei) was less in CH+A than CH (P <0.05). During in vitro hypoxia, the efficiency (ratio of ATP production/pressure x rate product) was the same in all groups and diazoxide had no measurable effects on myocardial performance, whereas glibenclamide increased end-diastolic pressure more in N and CH than in CH+A hearts (P <0.05). During reoxgenation, efficiency was markedly less in CH with respect to N and CH+A (P <0.0001), and rate x pressure product remained lower in CH than N and CH+A hearts (P <0.001), but glibenclamide or diazoxide abolished this difference. Glibenclamide, but not diazoxide, decreased vascular resistance in N and CH (P <0.005 and <0.001) without changes in CH+A. We hypothesize that cardioprotection in chronically hypoxic hearts derive from cell depolarization by sarcolemmal K + ATP blockade or from preservation of oxidative phosphorylation efficiency (ATP turnover/myocardial performance) by mitochondrial K+ ATP opening. Therefore K+ ATP channels are involved in the deleterious effects of chronic hypoxia and in the cardioprotection elicited when chronic hypoxia is interrupted with short normoxic aeration episodes.
|Number of pages||10|
|Journal||Experimental Biology and Medicine|
|Publication status||Published - Dec 2004|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)