CB₁ receptor activation in the rat paraventricular nucleus induces bi-directional cardiovascular effects via modification of glutamatergic and GABAergic neurotransmission

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• 作者：Emilia Grzęda ; Eberhard Schlicker…
• 关键词：Angiotensin AT1 receptor ; β2 ; adrenoceptor ; Cannabinoid CB1 receptor ; GABAA receptor ; NMDA receptor ; Paraventricular nucleus of hypothalamus
• 刊名：Naunyn-Schmiedeberg's Archives of Pharmacology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：390
• 期：1
• 页码：25-35
• 全文大小：1179KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Pharmacology/Toxicology; Neurosciences;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-1912
• 卷排序：390

文摘

We have shown previously that the cannabinoid receptor agonist CP55940 microinjected into the paraventricular nucleus of the hypothalamus (PVN) of urethane-anaesthetized rats induces depressor and pressor cardiovascular effects in the absence and presence of the CB₁ antagonist AM251, respectively. The aim of our study was to examine whether the hypotension and/or hypertension induced by CP55940 given into the PVN results from its influence on glutamatergic and GABAergic neurotransmission. CP55940 was microinjected into the PVN of urethane-anaesthetized rats twice (S₁ and S₂, 20 min apart). Antagonists of the following receptors, NMDA (MK801), β₂-adrenergic (ICI118551), thromboxane A₂–TP (SQ29548), angiotensin II–AT₁ (losartan) or GABA_A (bicuculline), or the NO synthase inhibitor L-NAME were administered intravenously 5 min before S₂ alone or together with AM251. The CP55940-induced hypotension was reversed into a pressor response by AM251, bicuculline and L-NAME, but not by the other antagonists. The CP55940-induced pressor effect examined in the presence of AM251 was completely reversed by losartan, reduced by about 50–60 % by MK801, ICI118551 and SQ29548, prevented by bilateral adrenalectomy but not modified by bicuculline and L-NAME. Parallel, but smaller, changes in heart rate accompanied the changes in blood pressure. The bi-directional CB₁ receptor-mediated cardiovascular effects of cannabinoids microinjected into the PVN of anaesthetized rats depend on stimulatory glutamatergic and inhibitory GABAergic inputs to the sympathetic tone; the glutamatergic input is related to AT₁, TP and β₂-adrenergic receptors and catecholamine release from the adrenal medulla whereas the GABAergic input is reinforced by NO.