This study was undertaken to clarify factors other than nitric oxide involved in reactive hyperemia after a short(30 sec) and a long(300 sec) coronary global no-flow ischemia in isolated rat hearts perfused at a constant pressure(90 mmHg) with special focuses on the contribution of various K channels including large and small conductance Ca-activated K(KCa) channels as well as ATP-sensitive K(KATP) channels. Reactive hyperemia was induced following 30 sec and 300 sec of no-flow ischemia of the heart. Coronary reactive hyperemia was observed even after the inhibition of nitric oxide synthase by N(ω)-nitro-L-arginine methyl ester(L-NAME). Selected K channel blockers, none of which affected the basal flow, were used to evaluate contribution of K channels to this L-NAME-resistant reactive hyperemia. After 30-sec ischemia, tetraethylammonium(TEA: a non-selective K channel blocker), glibenclamide(Gli: a KATP channel blocker) and α,β-methylene adenosine 5'-diphosphonate(AOPCP: an inhibitor of ecto 5'-nucleotidase) all suppressed both peak flow/basal flow(%PF) and repayment of flow debt(%RFD); After 300-sec ischemia, TEA and charybdotoxin(ChTX: a large conductance KCa channel blocker) decreased %PF and %RFD; AOPCP decreased both %RFD and duration, 4-aminopyridine(a voltage-dependent K channel blocker) decreased only duration. Neither apamin(a small conductance KCa channel blocker) nor indomethacin(a cyclooxygenase inhibitor) affected the both types of reactive hyperemia. These findings suggest that opening of KATP channel contributes to coronary vasodilation in reactive hyperemia after short 30-sec ischemia, and that opening of KCa, but not KATP, channel contributes to it after long 300-sec ischemia. These results also suggest that adenosine may partly be involved in both types of reactive hyperemia.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)