Affiliation:
1. Department of Pharmacology, University of Göteborg S-400 33 Göteborg 33, Sweden
Abstract
Abstract
Mean arterial blood pressure was recorded through in-dwelling arterial catheters in conscious normotensive Sprague-Dawley rats. L-3,4-Dihydroxyphenylalanine (L-dopa) was given in various doses intraperitoneally, alone and after pretreatment with an inhibitor of dopa decarboxylase, α-hydrazino-α-methyl-β-(3,4-dihydroxyphenyl) propionic acid (MK 485) or seryl-2,3,4-trihydroxybenzylhydrazine (Ro 4–4602). L-Dopa (50 mg/kg) produced a hypertensive response which was abolished by MK 485 (100 mg/kg). A larger dose of L-dopa (200 mg/kg) after MK 485 caused a significant lowering of blood pressure after 15–20 min. After Ro 4–4602 (400 + 200 mg/kg), injection of L-dopa (200 mg/kg) had no significant effect on blood pressure. The hypotensive response to L-dopa (200 mg/kg) after MK 485 was not influenced by the central dopamine receptor blocking agent, spiroperidol (0.1 mg/kg), but could be completely inhibited by the dopamine β-hydroxylase inhibitor, bis-(4-methyl-1-homopiperazinyl-thiocarbonyl)disulphide (FLA 63) (40 mg/kg). Pretreatment with protripty-line (10 mg/kg) completely blocked the hypotensive effect of L-dopa after MK 485. In correlative biochemical experiments, levels of noradrenaline and dopamine were determined in brain, heart and femoral muscle. L-Dopa (200 mg/kg) alone caused a significant increase of dopamine levels in all tissues. After MK 485 and Ro 4–4602 L-dopa did not significantly increase the levels of dopamine in heart or femoral muscle; however, brain dopamine levels were increased more than after L-dopa alone, but brain dopamine levels after Ro 4–4602 were significantly lower than after MK 485, indicating some central decarboxylase inhibition by Ro 4–4602. L-Dopa alone reduced the noradrenaline content of the heart and this effect was prevented by MK 485 and Ro 4–4602. The results show that decarboxylation of L-dopa in both the central and the peripheral nervous system leads to an increase in blood pressure. Decarboxylation of L-dopa in the central nervous system only results in a hypotensive response, provided that high amounts of dopamine are formed in the brain. This effect was prevented by an inhibitor of dopamine β-hydroxylase but not by a dopamine receptor blocker. Therefore, a central noradrenaline mechanism seems to be involved. The presence of an intact membrane pump in noradrenaline neurons may be essential since protriptyline also blocked the hypotensive action.
Publisher
Oxford University Press (OUP)
Subject
Pharmaceutical Science,Pharmacology
Cited by
101 articles.
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