Article date: December 2000
By: Kirsten Leineweber, Torsten Seyfarth, Otto‐Erich Brodde in Volume 131, Issue 7, pages 1438-1444
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 (uptake1) might undergo chamber‐specific alterations.
For this purpose we assessed in right and left ventricular slices, uptake1 activity (by [3H]‐noradrenaline accumulation), and in right and left ventricular membranes, uptake1 carrier protein density (by [3H]‐nisoxetine binding).
Uptake1‐inhibitors blocked [3H]‐noradrenaline accumulation in ventricular slices and [3H]‐nisoxetine binding in ventricular membranes with the order of potency: desipramine>nisoxetine>>cocaineGBR 12909, indicating that with both approaches noradrenaline uptake1 was determined.
In right ventricular slices of MCT‐treated rats uptake1 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 [3H]‐nisoxetine binding sites (73.7±14.4 vs 125.9±9.1 fmol mg−1 protein; P<0.05).
In left ventricular slices of MCT‐treated rats uptake1 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 [3H]‐nisoxetine binding sites was unchanged (108±9.7 vs 123±7.7 fmol mg−1 protein).
We conclude that in MCT‐treated rats with right ventricular hypertrophy and heart failure uptake1 activity is chamber‐specifically reduced possibly due to a decrease in carrier protein density.
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 (uptake1) might undergo chamber‐specific alterations.
For this purpose we assessed in right and left ventricular slices, uptake1 activity (by [3H]‐noradrenaline accumulation), and in right and left ventricular membranes, uptake1 carrier protein density (by [3H]‐nisoxetine binding).
Uptake1‐inhibitors blocked [3H]‐noradrenaline accumulation in ventricular slices and [3H]‐nisoxetine binding in ventricular membranes with the order of potency: desipramine>nisoxetine>>cocaineGBR 12909, indicating that with both approaches noradrenaline uptake1 was determined.
In right ventricular slices of MCT‐treated rats uptake1 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 [3H]‐nisoxetine binding sites (73.7±14.4 vs 125.9±9.1 fmol mg−1 protein; P<0.05).
In left ventricular slices of MCT‐treated rats uptake1 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 [3H]‐nisoxetine binding sites was unchanged (108±9.7 vs 123±7.7 fmol mg−1 protein).
We conclude that in MCT‐treated rats with right ventricular hypertrophy and heart failure uptake1 activity is chamber‐specifically reduced possibly due to a decrease in carrier protein density.
British Journal of Pharmacology (2000) 131, 1438–1444; doi:10.1038/sj.bjp.0703698
DOI: 10.1038/sj.bjp.0703698
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