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

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 chambe r-specific alterations. 2 For this purpose we assessed in right and left ventricular slices, uptake (1) activity (by [H-3]noradrenaline accumulation), and in right and left ve ntricular membranes. uptake(1) carrier protein density (by [H-3]-nisoxetine binding). 3 Uptake(1)-inhibitors blocked [H-3]-noradrenaline accumulation in ventricu lar slices and [H-3]- nisoxetine binding in ventricular membranes with the order of potency: desipramine > nisoxetine>>cocaine greater than or equal t o GBR 12909, indicating that with both approaches noradrenaline uptake(1) w as determined. 4 In right ventricular slices of MCT-treated rats uptake(1) activity was si gnificantly 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 [H-3]-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 [H-3]-nisoxetine bind ing 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 a nd heart failure uptake(1) activity is chamber-specifically reduced possibl y due to a decrease in carrier protein density.