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THE CARDIOVASCULAR EFFECTS OF l ‐DOPA IN THE PITHED RAT
Author(s) -
EDEN E.,
NASMYTH P.A.
Publication year - 1974
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1974.tb09664.x
Subject(s) - dopamine , perfusion , norepinephrine , medicine , endocrinology , aromatic l amino acid decarboxylase , chemistry , intravenous infusions , pressor response , decarboxylase inhibitor , catecholamine , blood pressure , pharmacology , levodopa , heart rate , parkinson's disease , disease
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.