Peripherally administered gamma-aminobutyric acid (GABA) alters cardio
vascular function and has been reported to enhance ouabain-induced car
diotoxicity in vivo. Control and reserpinized rat hearts were perfused
in vitro to determine if GABA directly evokes bradycardia by GABA(A)
receptors, interacts with ouabain, and if noradrenergic mechanisms are
required. Also, double-staining immunohistochemistry was employed to
determine whether GABA-ergic and noradrenergic synthetic enzymes were
juxtaposed within atrial tissue. The main results were as follows. GAB
A produced a dose-dependent bradycardia (p < 0.05) by stimulating GABA
(A) receptors in Langendorff-perfused hearts. Reserpinized hearts were
unresponsive (p > 0.05) to GABA, except at the highest dose (20 mg/ml
). Oubain-induced cardiotoxicity was enhanced (p < 0.05) by GABA in is
olated control, but not reserpinized hearts. Lastly, glutamic acid dec
arboxylase and tyrosine hydroxylase immunoreactivities were in close p
roximity in atrial slices. Collectively, the results document that GAB
A causes bradycardia and enhances ouabain cardiotoxicity by modulating
noradrenergic mechanisms in the isolated rat heart. Since the synthet
ic enzymes for GABA and norepinephrine were in close proximity in atri
al tissue, these transmitters may interact under physiological conditi
ons.