DIFFERENCE IN HYPOTENSIVE RESPONSE TO L-DOPA AND A DECARBOXYLASE INHIBITOR IN VARIOUS FORMS OF HYPERTENSIVE RATS

[摘要] References(32)Cited-By(2)In unanesthetized and unrestraint rats, the administration of L-DOPA (20 mg/kg i.p.) with a peripheral decarboxylase inhibitor, Ro 4-4602 (50 mg/kg i.p.), markedly lowered blood pressure in DOCA-salt hypertensive rats (DHR) much more than it did in spontaneously hypertensive rats (SHR) or three types of normotensive controls; normal (NR), uninephrectomied and DOCA only. L-DOPA plus Ro 4-4602 did not change the renal hypertension induced by clipping a renal artery and uninephrectomy (RHR). The marked fall in blood pressure of DHR after L-DOPA plus Ro 4-4602 seemed to correlate with the accumulation of dopamine in the medullapons and hypothalamus, and of DOPA content in the medulla-pons. In RHR, accumulation of dopamine in the medulla-pons and hypothalamus was markedly lower than that in DHR, SHR and NR. Bilateral destruction of dopaminergic neurons in the striatum with 6-hydroxydopamine did not change blood pressure lowering activity of L-DOPA Plus Ro 4-4602 in NR and DHR. Spiroperidol (0.01 mg/kg i.p. × 2) caused no effect on the fall in blood pressure of DHR after L-DOPA plus Ro 4-4602, whereas the same doses of spiroperidol reduced amantadine-induced stereotyped behavior in DHR. These data suggest that the pronounced fall in blood pressure of DHR after L-DOPA plus Ro 4-4602 may be related to the marked accumulation of DA or DOPA in the brainstem, most probably in its noradrenergic neurons, but involvement of DA neurons per se may be minimal. Hypotensive reactivity of brainstem neurons with the DA accumulation is in the order of; DHR>SHR=NR>RHR.

[学科分类] 药理学