THE CARDIOVASCULAR EFFECTS OF l‐DOPA IN THE PITHED RAT

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Abstract
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 μg 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-β-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 μg 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 μg 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 μg kg−1 min−1) or of l-DOPA (200 μg 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.