T Akiyama1, T Yamazaki. 1. Department of Cardiac Physiology, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, 565-8565, Osaka, Japan.takiyama@ri.ncvc.go.jp
Abstract
OBJECTIVE: The aim was to elucidate the relation between norepinephrine (NE) release and intraneuronal NE kinetics in the ischemic region of the in vivo heart. METHODS: Using dialysis technique in the heart of anesthetized cats, we sampled dialysate from the ischemic region during 120-min coronary occlusion and reperfusion. Dialysate NE and dihydroxyphenylglycol (DHPG) contents were measured as indexes of myocardial interstitial NE and DHPG levels. RESULTS: Within 20 min of occlusion, interstitial NE levels increased while DHPG levels decreased. This NE increase was suppressed by omega-conotoxin GVIA and enhanced by desipramine. These data suggest that axoplasmic NE levels increased by neuronal reuptake following exocytotic release, while intraneuronal DHPG production was suppressed due to the reduced monoamine oxidase activity. After 20 min of occlusion, interstitial NE levels increased markedly, accompanied by increased DHPG levels. This NE increase was suppressed by desipramine. These findings imply that NE mobilization from stored vesicles to axoplasma exceeded outward NE transport through uptake(1) carrier in the amount of NE, and that a substantial increase in axoplasmic NE levels compensated for the reduced monoamine oxidase activity. After reperfusion, interstitial NE levels rapidly decreased while DHPG levels increased further. Both responses in NE and DHPG were suppressed by desipramine, indicating the involvement of recovered neuronal reuptake function. CONCLUSIONS: In the ischemic region, intraneuronal DHPG production was affected by alterations in monoamine oxidase activity, NE mobilization from stored vesicles, and carrier-mediated NE transport. The involvement of these factors in intraneuronal NE kinetics varied with the time of occlusion and reperfusion.
OBJECTIVE: The aim was to elucidate the relation between norepinephrine (NE) release and intraneuronal NE kinetics in the ischemic region of the in vivo heart. METHODS: Using dialysis technique in the heart of anesthetized cats, we sampled dialysate from the ischemic region during 120-min coronary occlusion and reperfusion. Dialysate NE and dihydroxyphenylglycol (DHPG) contents were measured as indexes of myocardial interstitial NE and DHPG levels. RESULTS: Within 20 min of occlusion, interstitial NE levels increased while DHPG levels decreased. This NE increase was suppressed by omega-conotoxin GVIA and enhanced by desipramine. These data suggest that axoplasmic NE levels increased by neuronal reuptake following exocytotic release, while intraneuronal DHPG production was suppressed due to the reduced monoamine oxidase activity. After 20 min of occlusion, interstitial NE levels increased markedly, accompanied by increased DHPG levels. This NE increase was suppressed by desipramine. These findings imply that NE mobilization from stored vesicles to axoplasma exceeded outward NE transport through uptake(1) carrier in the amount of NE, and that a substantial increase in axoplasmic NE levels compensated for the reduced monoamine oxidase activity. After reperfusion, interstitial NE levels rapidly decreased while DHPG levels increased further. Both responses in NE and DHPG were suppressed by desipramine, indicating the involvement of recovered neuronal reuptake function. CONCLUSIONS: In the ischemic region, intraneuronal DHPG production was affected by alterations in monoamine oxidase activity, NE mobilization from stored vesicles, and carrier-mediated NE transport. The involvement of these factors in intraneuronal NE kinetics varied with the time of occlusion and reperfusion.
Authors: Attila Kiss; Ping Wu; Michaela Schlederer; Patrick M Pilz; Petra Lujza Szabo; Jingle Li; Lukas Weber; Chrysoula Vraka; Verena Pichler; Markus Mitterhauser; Xiaoli Zhang; Karin Zins; Dietmar Abraham; Sijin Li; Bruno K Podesser; Marcus Hacker; Xiang Li Journal: Basic Res Cardiol Date: 2022-08-25 Impact factor: 12.416