3-(2-hydroxy-4-(1-1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol has been researched along with methylatropine* in 2 studies
2 other study(ies) available for 3-(2-hydroxy-4-(1-1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol and methylatropine
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The peripheral sympathetic nervous system is the major target of cannabinoids in eliciting cardiovascular depression.
Our objective was to identify the sites of interaction of cannabinoids with cardiovascular sympathetic regulation in the rat. Effects on sympathetic tone were first determined in anaesthetised animals following i.v. administration of the drugs. Central effects were evaluated in anaesthetised rats receiving microinjections of cannabinoids into brain stem nuclei. Peripheral effects were identified in pithed rats with electrically stimulated sympathetic outflow. In anaesthetised and artificially ventilated rats, i.v. injection of the cannabinoid agonists WIN55212-2 and CP55940 decreased mean arterial pressure, heart rate and the plasma noradrenaline concentration. These effects were antagonized by the CB(1) cannabinoid receptor antagonist SR141716A. The bradycardia was abolished by the muscarinic acetylcholine receptor antagonist methylatropine. The decreases in mean arterial pressure and heart rate caused by cannabinoids in ventilated rats were much less pronounced than in spontaneously breathing rats. Microinjection of WIN55212-2 into the nucleus tractus solitarii had no effect. Microinjected into the rostral ventrolateral medulla oblongata, WIN55212-2 lowered mean arterial pressure slightly without changing other parameters. In pithed rats, WIN55212-2 inhibited the increases in mean arterial pressure, heart rate and the plasma noradrenaline concentration evoked by electrical stimulation of the sympathetic outflow. Our results show that activation of CB(1) cannabinoid receptors induces sympathoinhibition and enhancement of cardiac vagal tone, leading to hypotension and bradycardia. Presynaptic inhibition of noradrenaline release from terminals of postganglionic sympathetic neurons is the major component of the sympathoinhibition, but an effect in the rostral ventrolateral medulla oblongata may also contribute. The cannabinoid-evoked cardiovascular depression depends strongly on the respiratory state of the animals. Topics: Animals; Atropine Derivatives; Benzoxazines; Bradycardia; Cannabinoids; Cardiovascular System; Cyclohexanols; Disease Models, Animal; Dose-Response Relationship, Drug; Hypotension; Male; Medulla Oblongata; Microinjections; Morpholines; Naphthalenes; Norepinephrine; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Rimonabant; Sympathetic Fibers, Postganglionic; Sympathetic Nervous System | 2003 |
Analysis of the respiratory effects of cannabinoids in rats.
The objective of the present study was to evaluate the respiratory effects of cannabinoids and their influence on cardiovascular homeostasis.In spontaneously breathing urethane-anaesthetised rats, intravenous injection of the two synthetic cannabinoid receptor agonists WIN55212-2 and CP55940 strongly and dose-dependently lowered mean arterial pressure, heart rate and the plasma noradrenaline concentration. The cardiovascular depressive effects were associated with a large decrease in respiratory rate, hypoxia, hypercapnia and blood acidosis. All depressor effects of WIN55212-2 were abolished by the selective CB(1) cannabinoid receptor antagonist SR141716A. The bradycardia elicited by WIN55212-2 was inhibited by the muscarinic acetylcholine receptor antagonist methylatropine. The natural agonist Delta(9)-tetrahydrocannabinol also elicited cardiovascular and respiratory depression. In contrast, WIN55212-3, an enantiomer of WIN55212-2 lacking affinity for cannabinoid receptors, had no effect. The cannabinoid-evoked decreases in blood pressure and heart rate were much more pronounced in spontaneously breathing than in artificially ventilated urethane-anaesthetised rats. In contrast, the plasma noradrenaline concentration was lowered equally in both preparations. Our results show that activation of CB(1) cannabinoid receptors not only induces cardiovascular depression, but also markedly impairs ventilation. The second major finding of the present study is that the respiratory depression evoked by cannabinoids largely amplifies the cardiovascular depression. Topics: Anesthesia; Animals; Atropine Derivatives; Benzoxazines; Blood Pressure; Cannabinoids; Cyclohexanols; Depression, Chemical; Dronabinol; Heart Rate; Hemodynamics; Morpholines; Muscarinic Agonists; Naphthalenes; Norepinephrine; Oxygen Consumption; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Respiration, Artificial; Respiratory Mechanics | 2003 |