title: CB1receptor activation in the rat paraventricular nucleus induces bi-directional cardiovascular effects via modification of glutamatergic and GABAergic neurotransmission.
abstract: 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 CB1antagonist 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 (S1and S2, 20 min apart). Antagonists of the following receptors, NMDA (MK801), β2-adrenergic (ICI118551), thromboxane A2-TP (SQ29548), angiotensin II-AT1(losartan) or GABAA(bicuculline), or the NO synthase inhibitor L-NAME were administered intravenously 5 min before S2alone 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 CB1receptor-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.
authors.affiliation: Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Grzęda
authors.affiliation: Department of Pharmacology and Toxicology, University of Bonn, Bonn, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schlicker
authors.affiliation: Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Toczek
authors.affiliation: Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Zalewska
authors.affiliation: Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Baranowska-Kuczko
authors.affiliation: Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland. bmalin@umb.edu.pl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Malinowska
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage / Q000633:toxicity*; D003511:Cyclohexanols / Q000008:administration & dosage / Q000633:toxicity*; D018698:Glutamic Acid / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D007022:Hypotension / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008845:Microinjections; D009433:Neural Inhibition / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D063386:Cannabinoid Receptor Agonists; C543264:Cnr1 protein, rat; D003511:Cyclohexanols; D044140:Receptor, Angiotensin, Type 1; D043884:Receptor, Cannabinoid, CB1; D018343:Receptors, Adrenergic, beta-2; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D009569:Nitric Oxide; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
keywords: Angiotensin AT1 receptor; Cannabinoid CB1 receptor; GABAA receptor; NMDA receptor; Paraventricular nucleus of hypothalamus; β2-adrenoceptor