| First Author | Zhou X | Year | 2014 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 307 |
| Issue | 7 | Pages | H1046-55 |
| PubMed ID | 25108010 | Mgi Jnum | J:218325 |
| Mgi Id | MGI:5617302 | Doi | 10.1152/ajpheart.00421.2014 |
| Citation | Zhou X, et al. (2014) Metabolic hyperemia requires ATP-sensitive K+ channels and H2O2 but not adenosine in isolated mouse hearts. Am J Physiol Heart Circ Physiol 307(7):H1046-55 |
| abstractText | We have previously demonstrated that adenosine-mediated H2O2 production and opening of ATP-sensitive K(+) (KATP) channels contributes to coronary reactive hyperemia. The present study aimed to investigate the roles of adenosine, H2O2, and KATP channels in coronary metabolic hyperemia (MH). Experiments were conducted on isolated Langendorff-perfused mouse hearts using combined pharmacological approaches with adenosine receptor (AR) knockout mice. MH was induced by electrical pacing at graded frequencies. Coronary flow increased linearly from 14.4 +/- 1.2 to 20.6 +/- 1.2 ml.min(-1).g(-1) with an increase in heart rate from 400 to 650 beats/min in wild-type mice. Neither non-selective blockade of ARs by 8-(p-sulfophenyl)theophylline (8-SPT; 50 muM) nor selective A2AAR blockade by SCH-58261 (1 muM) or deletion affected MH, although resting flow and left ventricular developed pressure were reduced. Combined A2AAR and A2BAR blockade or deletion showed similar effects as 8-SPT. Inhibition of nitric oxide synthesis by N-nitro-l-arginine methyl ester (100 muM) or combined 8-SPT administration failed to reduce MH, although resting flows were reduced (by approximately 20%). However, glibenclamide (KATP channel blocker, 5 muM) decreased not only resting flow (by approximately 45%) and left ventricular developed pressure (by approximately 36%) but also markedly reduced MH by approximately 94%, resulting in cardiac contractile dysfunction. Scavenging of H2O2 by catalase (2,500 U/min) also decreased resting flow (by approximately 16%) and MH (by approximately 24%) but to a lesser extent than glibenclamide. Our results suggest that while adenosine modulates coronary flow under both resting and ischemic conditions, it is not required for MH. However, H2O2 and KATP channels are important local control mechanisms responsible for both coronary ischemic and metabolic vasodilation. |
