| First Author | Headrick JP | Year | 2000 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 279 |
| Issue | 4 | Pages | H1690-7 |
| PubMed ID | 11009456 | Mgi Jnum | J:65227 |
| Mgi Id | MGI:1913222 | Doi | 10.1152/ajpheart.2000.279.4.H1690 |
| Citation | Headrick JP, et al. (2000) Cardioprotection by K(ATP) channels in wild-type hearts and hearts overexpressing A(1)-adenosine receptors. Am J Physiol Heart Circ Physiol 279(4):H1690-7 |
| abstractText | We studied the role of mitochondrial ATP-sensitive K(+) (K(ATP)) channels in modifying functional responses to 20 min global ischemia and 30 min reperfusion in wild-type mouse hearts and in hearts with approximately 250-fold overexpression of functionally coupled A(1)-adenosine receptors (A(1)ARs). In wild-type hearts, time to onset of contracture (TOC) was 303 +/- 24 s, with a peak contracture of 89 +/- 5 mmHg. Diastolic pressure remained elevated at 52 +/- 6 mmHg after reperfusion, and developed pressure recovered to 40 +/- 6% of preischemia. A(1)AR overexpression markedly prolonged TOC to 517 +/- 84 s, reduced contracture to 64 +/- 6 mmHg, and improved recovery of diastolic (to 9 +/- 4 mmHg) and developed pressure (to 82 +/- 8%). 5-Hydroxydecanoate (5-HD; 100 &mgr;M), a mitochondrial K(ATP) blocker, did not alter ischemic contracture in wild-type hearts, but increased diastolic pressure to 69 +/- 8 mmHg and reduced developed pressure to 10 +/- 5% during reperfusion. In transgenic hearts, 5-HD reduced TOC to 348 +/- 18 s, increased postischemic contracture to 53 +/- 4 mmHg, and reduced recovery of developed pressure to 22 +/- 4%. In summary, these data are the first to demonstrate that endogenous activation of K(ATP) channels improves tolerance to ischemia-reperfusion in murine myocardium. This functional protection occurs without modification of ischemic contracture. The data also support a role for mitochondrial K(ATP) channel activation in the pronounced cardioprotection afforded by overexpression of myocardial A(1)ARs. |
