Myocardial interstitial serotonin and its major metabolite, 5-hydroxyindole acetic acid levels determined by microdialysis technique in rat heart

Aims

The aim of this study was to elucidate myocardial interstitial serotonin (5-HT) kinetics in the heart, including 5-HT reuptake and enzymatic degradation to 5-hydroxyindole acetic acid (5-HIAA) via monoamine oxidase (MAO).

Main methods

Using microdialysis technique in anesthetized rats, we simultaneously monitored myocardial interstitial levels of 5-HT and its major metabolite, 5-HIAA, in the left ventricle and examined the effects of local administration of a MAO inhibitor, pargyline, or a 5-HT uptake inhibitor, fluoxetine.

Key findings

Pargyline increased dialysate 5-HT concentration from 1.8 ± 0.3 at baseline to 3.9 ± 0.5 nM but decreased dialysate 5-HIAA concentration from 20.7 ± 1.0 at baseline to 15.8 ± 1.4 nM at 60–80 min of administration. Fluoxetine increased dialysate 5-HT concentration from 1.9 ± 0.4 at baseline to 6.5 ± 0.9 nM at 60–80 min of administration, but did not change dialysate 5-HIAA concentration. Local administration of ADP (100 mM) increased dialysate 5-HT and 5-HIAA concentrations. Pargyline did not affect ADP-induced increase in dialysate 5-HT concentration but suppressed ADP-induced increase in dialysate 5-HIAA concentration during 60 min of ADP administration. Fluoxetine increased dialysate 5-HT concentration at 40–60 min of ADP administration, but did not affect ADP-induced increase in dialysate 5-HIAA concentration.

Significance

Simultaneous monitoring of myocardial interstitial 5-HT and 5-HIAA levels provides valuable information on 5-HT kinetics including reuptake and enzymatic degradation by MAO, which play a role in the regulation of myocardial interstitial 5-HT levels at baseline and when 5-HT levels are elevated.