Chamber‐specific alterations of noradrenaline uptake (uptake 1 ) in right ventricles of monocrotaline‐treated rats

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. 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). 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>>cocaineGBR 12909, indicating that with both approaches noradrenaline uptake 1 was determined. 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). 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). 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.British Journal of Pharmacology (2000) 131 , 1438–1444; doi: 10.1038/sj.bjp.0703698