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Chamber-specific alterations of noradrenaline uptake (uptake(1)) in right ventricles of monocrotaline-treated rats.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 2000 Dec; Vol. 131 (7), pp. 1438-44. - Publication Year :
- 2000
-
Abstract
- 1. In rats a single injection of the alkaloid monocrotaline (60 mg MCT kg(-1) body weight, i.p.) caused right ventricular hypertrophy and heart failure. The aim of this study was to find out whether, in these MCT-treated rats, the cardiac neuronal noradrenaline uptake (uptake(1)) might undergo chamber-specific alterations. 2. For this purpose we assessed in right and left ventricular slices, uptake(1) activity (by [(3)H]-noradrenaline accumulation), and in right and left ventricular membranes, uptake(1) carrier protein density (by [(3)H]-nisoxetine binding). 3. Uptake(1)-inhibitors blocked [(3)H]-noradrenaline accumulation in ventricular slices and [(3)H]-nisoxetine binding in ventricular membranes with the order of potency: desipramine > nisoxetine >> cocaine > or = GBR 12909, indicating that with both approaches noradrenaline uptake(1) was determined. 4. In right ventricular slices of MCT-treated rats uptake(1) activity was significantly lower than in control rats (84.7+/-8.2 vs 145.1+/-6.2 pmol noradrenaline mg(-1) tissue 15 min(-1); P<0.05). This was accompanied by a significant decrease in the density of [(3)H]-nisoxetine binding sites (73.7+/-14.4 vs 125.9+/-9.1 fmol mg(-1) protein; P:<0.05). 5. In left ventricular slices of MCT-treated rats uptake(1) activity was not significantly altered (131.2+/-10.5 vs 116.1+/-5.2 pmol noradrenaline mg(-1) tissue 15 min(-1)); similarly, also the density of [(3)H]-nisoxetine binding sites was unchanged (108+/-9.7 vs 123+/-7.7 fmol mg(-1) protein). 6. We conclude that in MCT-treated rats with right ventricular hypertrophy and heart failure uptake(1) activity is chamber-specifically reduced possibly due to a decrease in carrier protein density.
- Subjects :
- Adrenergic Uptake Inhibitors pharmacology
Animals
Binding, Competitive drug effects
Cocaine pharmacology
Desipramine pharmacology
Dopamine Uptake Inhibitors pharmacology
Dose-Response Relationship, Drug
Fluoxetine analogs & derivatives
Fluoxetine metabolism
Fluoxetine pharmacology
Heart Failure chemically induced
Heart Failure metabolism
Heart Ventricles metabolism
Heart Ventricles pathology
Hypertrophy
In Vitro Techniques
Male
Membranes drug effects
Membranes metabolism
Norepinephrine antagonists & inhibitors
Piperazines pharmacology
Rats
Rats, Wistar
Tritium
Heart Ventricles drug effects
Monocrotaline pharmacology
Norepinephrine pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 0007-1188
- Volume :
- 131
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 11090118
- Full Text :
- https://doi.org/10.1038/sj.bjp.0703698