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

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概要

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• 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 <I>per se</I> may be minimal. Hypotensive reactivity of brainstem neurons with the DA accumulation is in the order of; DHR>SHR=NR>RHR.

• 社団法人 日本薬理学会の論文

著者

• Mizogami Susumu

  Department Of Pharmacology Toho University School Of Medicine:(presuent Address)research Laboratory

• NAKAMURA Keiji

  Nippon Roche Research Center

• NAKAMURA Kazuo

  Nippon Roche Research Center

• MIZOGAMI Susumu

  Department of Pharmacology, Toho University School of Medicine

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• MECHANISMS OF CENTRAL HYPOTENSIVE ACTIVITY OF L-DOPA AND A PERIPHERAL DECARBOXYLASE INHIBITOR IN DOCA-SALT HYPERTENSIVE RATS
• DIFFERENCE IN HYPOTENSIVE RESPONSE TO L-DOPA AND A DECARBOXYLASE INHIBITOR IN VARIOUS FORMS OF HYPERTENSIVE RATS
• Reactivity of Norepinephrine Receptors in the Cardiovascular System of Hypertensive Rats
• Cardiovascular Reactivity in Hypertensive Rats
• Cardiovascular Reactivity after Bilateral Nephrectomy in Rats
• Further Studies on the Mechanisms of Blood Pressure Lowering Effect of L-DOPA and a Peripheral Decarboxylase Inhibitor in Hypertensive Rats

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