The cardiovascular effects of L-dopa in the pithed rat

1 L-DOPA (1-2 mg i.v.) in the pithed rat reduced the arterial and increased the venous pressure responses to noradrenaline.2 Infusions of dopamine (4-8 mug kg(-1) min(-1)) and noradrenaline (500 ng kg(-1) min(-1)) also reduced the pressor responses to noradrenaline. The pressor response did not recover after stopping dopamine infusions, but it usually did so after stopping noradrenaline infusions.3 The effect of L-DOPA on the response to noradrenaline was prevented by the prior injection of the dopa decarboxylase inhibitor NSD 1024.4 The prior injection of the dopamine-beta-hydroxylase inhibitor diethyldithiocarbamate, only partially prevented the effect of L-DOPA on pressor responses to noradrenaline.5 The perfusion of noradrenaline (400 ng kg(-1) min(-1)) together with Krebs solution (10 ml/min) through an organ bath containing an isolated aortic strip, depressed the response of the strip to doses of noradrenaline after the infusion was stopped. Infusions of dopamine (0.5-8.0 mug kg(-1) min(-1)) had a similar effect. Fifteen minutes after adding L-DOPA (0.5 mg) to the bath and 10 min after washing it out, the response to noradrenaline was depressed in three out of four experiments.6 Infusions of noradrenaline (1 mug kg(-1) min(-1)) in an isolated heart perfused by Langendorf's method blocked the response to injected noradrenaline whilst perfusion was in progress. Infusions of dopamine (4-8 mug kg(-1) min(-1)) or of L-DOPA (200 mug kg(-1) min(-1)) did not have this effect.7 It is concluded that the effect of L-DOPA on pressor responses to noradrenaline in the pithed rat are mediated by its conversion to dopamine and noradrenaline.