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Cardiac noradrenergic mechanisms mediate GABA-enhanced ouabain cardiotoxicity.
- Source :
-
Pharmacology [Pharmacology] 1994 Dec; Vol. 49 (6), pp. 343-50. - Publication Year :
- 1994
-
Abstract
- Peripherally administered gamma-aminobutyric acid (GABA) alters cardiovascular function and has been reported to enhance ouabain-induced cardiotoxicity in vivo. Control and reserpinized rat hearts were perfused in vitro to determine if GABA directly evokes bradycardia by GABAA 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. GABA produced a dose-dependent bradycardia (p < 0.05) by stimulating GABAA receptors in Langendorff-perfused hearts. Reserpinized hearts were unresponsive (p < 0.05) to GABA, except at the highest dose (20 mg/ml). Ouabain-induced cardiotoxicity was enhanced (p < 0.05) by GABA in isolated control, but not reserpinized hearts. Lastly, glutamic acid decarboxylase and tyrosine hydroxylase immunoreactivities were in close proximity in atrial slices. Collectively, the results document that GABA causes bradycardia and enhances ouabain cardiotoxicity by modulating noradrenergic mechanisms in the isolated rat heart. Since the synthetic enzymes for GABA and norepinephrine were in close proximity in atrial tissue, these transmitters may interact under physiological conditions.
- Subjects :
- Analysis of Variance
Animals
Bradycardia chemically induced
Bradycardia metabolism
Dose-Response Relationship, Drug
Glutamate Decarboxylase metabolism
Rats
Rats, Inbred F344
Rats, Sprague-Dawley
Rats, Wistar
Reserpine pharmacology
Tyrosine 3-Monooxygenase metabolism
Heart drug effects
Myocardium metabolism
Norepinephrine physiology
Ouabain pharmacology
Receptors, GABA-A metabolism
gamma-Aminobutyric Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0031-7012
- Volume :
- 49
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 7878072
- Full Text :
- https://doi.org/10.1159/000139253