Effects of anoxia and ischemia on uptake2 of catecholamines in perfused rat heart.

The effects of 30 min periods of either anoxia or ischemia (stop-flow) on the uptake2 of isoprenaline and on the production of O-methyl-isoprenaline, a major metabolite of isoprenaline formed by catechol-O-methyltransferase (COMT), were examined in the perfused rat heart. After either glucose deprivation or anoxia, the uptake2 of isoprenaline in hearts subsequently perfused with isoprenaline and 3',4'-dihydroxy-2-methyl-propiophenone, a COMT inhibitor, was similar to control values. However, uptake2 was decreased following either anoxia in association with glucose deprivation or ischemia. In the absence of the COMT inhibitor, neither glucose deprivation nor anoxia alone had any effect on the production of [3H]3-O-methyl-isoprenaline from [3H]isoprenaline, but both anoxia together with glucose deprivation and stop-flow ischemia decreased it. These findings indicate that both anoxia coupled with glucose deprivation and ischemia inhibit both uptake2 and COMT activity and suggest that such inhibition may be responsible for the high concentration of catecholamines released locally following myocardial infarction.