methylatropine and Hypotension

Cardiovascular effects of the linalool-rich essential oil of Aniba rosaeodora (here named as EOAR) in normotensive rats were investigated. In anesthetized rats, intravenous (i.v.) injection of EOAR induced dose-dependent biphasic hypotension and bradycardia. Emphasis was given to the first phase (phase 1) of the cardiovascular effects, which is rapid (onset time of 1-3 s) and not observed in animals submitted to bilateral vagotomy or selective blockade of neural conduction of vagal C-fibre afferents by perineural treatment with capsaicin. Phase 1 was also absent when EOAR was directly injected into the left ventricle injection, but it was unaltered by i.v. pretreatment with capsazepine, ondansetron or HC030031. In conscious rats, EOAR induced rapid and monophasic hypotensive and bradycardiac (phase 1) effects that were abolished by i.v. methylatropine. In endothelium-intact aortic rings, EOAR fully relaxed phenylephrine-induced contractions in a concentration-dependent manner. The present findings reveal that phase 1 of the bradycardiac and depressor responses induced by EOAR has a vago-vagal reflex origin resulting from the vagal pulmonary afferents stimulation. Such phenomenon appears not to involve the recruitment of C-fibre afferents expressing 5HT3 receptors or the two chemosensory ion channels TRPV1 and TRPA1 . Phase 2 hypotensive response appears resulting from a direct vasodilatory action.

Topics: Acetanilides; Acyclic Monoterpenes; Animals; Aorta; Atropine Derivatives; Blood Pressure; Bradycardia; Capsaicin; Hypotension; In Vitro Techniques; Lauraceae; Male; Monoterpenes; Oils, Volatile; Ondansetron; Phenylephrine; Plant Oils; Purines; Rats; Rats, Wistar; Reflex

Previously, it was shown that intravenous (i.v.) treatment with the essential oil of Aniba canelilla (EOAC) elicited a hypotensive response that is due to active vascular relaxation rather than to the withdrawal of sympathetic tone. The present study investigated mechanisms underlying the cardiovascular responses to 1-nitro-2-phenylethane, the main constituent of the EOAC. In pentobarbital-anesthetized normotensive rats, 1-nitro-2-phenylethane (1-10mg/kg, i.v.) elicited dose-dependent hypotensive and bradycardiac effects which were characterized in two periods (phases 1 and 2). The first rapid component (phase 1) evoked by 1-nitro-2-phenylethane (10mg/kg) was fully abolished by bilateral vagotomy, perineural treatment of both cervical vagus nerves with capsaicin (250 microg/ml) and was absent after left ventricle injection. However, pretreatment with capsazepine (1mg/kg, i.v.) or ondansetron (30 microg/kg, i.v.) did not alter phase 1 of the cardiovascular responses to 1-nitro-2-phenylethane (10mg/kg, i.v.). In conscious rats, 1-nitro-2-phenylethane (1-10mg/kg, i.v.) evoked rapid hypotensive and bradycardiac (phase 1) effects that were fully abolished by methylatropine (1mg/kg, i.v.). It is concluded that 1-nitro-2-phenylethane induces a vago-vagal bradycardiac and depressor reflex (phase 1) that apparently results from the stimulation of vagal pulmonary rather than cardiac C-fiber afferents. The transduction mechanism of the 1-nitro-2-phenylethane excitation of C-fiber endings is not fully understood and does not appear to involve activation of either Vanilloid TPRV(1) or 5-HT(3) receptors. The phase 2 hypotensive response to 1-nitro-2-phenylethane seems to result, at least in part, from a direct vasodilatory effect since 1-nitro-2-phenylethane (1-300 microg/ml) induced a concentration-dependent reduction of phenylephrine-induced contraction in rat endothelium-containing aorta preparations.

Topics: Animals; Aorta; Atropine Derivatives; Benzene Derivatives; Bradycardia; Capsaicin; Cryptocarya; Dose-Response Relationship, Drug; Herb-Drug Interactions; Hypotension; In Vitro Techniques; Male; Oils, Volatile; Ondansetron; Phenylephrine; Rats; Rats, Wistar; Reflex; Vagus Nerve; Vasoconstriction

An increase in endogenous central histamine concentration after inhibition of histamine N-methyltransferase (HNMT) activity reverses critical hypotension and improves the survival of rats in haemorrhagic shock. The purpose of the study was to examine the involvement of the sympathetic nervous system in this endogenous central histamine-induced resuscitation. Experiments were carried out in ethylurethane-anaesthetised male Wistar rats subjected to haemorrhagic hypotension (mean arterial pressure MAP 20-25 mmHg), which led to the death of all control animals within 30 min. The HNMT inhibitor metoprine (20 micro g; i.c.v.) administered 5 min after establishing the critical hypotension increased the endogenous histamine concentration, measured 20 min after treatment, in the hypothalamus (534.33+/-67.52 vs. 423.98+/-54.17 ng/g wet tissue; P<0.05) and medulla oblongata (53.12+/-9.78 vs. 39.58+/-11.16 ng/g wet tissue; P<0.05). These responses were accompanied by plasma levels of noradrenaline and adrenaline 2.7 and 1.7 times higher respectively than in the control group ( P<0.01). Metoprine evoked dose-dependent (5, 10, 20 micro g; i.c.v.) rises in MAP and heart rate (HR) that were significantly higher than those in normotensive animals, and resulted in a 100% survival rate at 2 h after treatment (20 micro g; i.c.v.). The resuscitative effect was associated with rises in renal, hindquarters and mesenteric blood flows. The nicotinic cholinoceptor antagonist hexamethonium (3 mg/kg; i.v.) attenuated the MAP and HR changes, whereas the muscarinic cholinoceptor blocker methylatropine (2 mg/kg; i.v.) attenuated only the pressor effect. Metoprine-induced MAP and regional haemodynamic effects were also reduced by alpha(1)- and alpha(2)-adrenoceptor antagonists prazosin (0.5 mg/kg; i.v.) and yohimbine (1 mg/kg; i.v.), while the beta-adrenoceptor blocker propranolol (1 mg/kg; i.v.) diminished only HR changes. Ganglionic transmission inhibitors and adrenoceptor antagonists did not influence the survival rate at 2 h in the metoprine-treated groups. Bilateral adrenal demedullation diminished the pressor effect of metoprine, however, without influence on HR and survival at 2 h after treatment. In conclusion, the study demonstrates the activation of the sympathetic nervous system elicited by endogenous central histamine in haemorrhage-shocked rats and confirms its involvement in histamine-induced resuscitation.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Animals; Atropine Derivatives; Blood Pressure; Brain; Dose-Response Relationship, Drug; Epinephrine; Heart Rate; Hexamethonium; Histamine; Histamine N-Methyltransferase; Hypotension; Male; Muscarinic Antagonists; Nicotinic Antagonists; Pyrimethamine; Rats; Rats, Wistar; Regional Blood Flow; Shock, Hemorrhagic; Sympathetic Nervous System

The present study investigated the mechanisms by which intrathecal (i.t.) apomorphine affects mean aortic pressure and heart rate in anesthetized rats. In saline-pretreated rats, upper thoracic (T2-T4) i.t. administration of apomorphine (48 microg/rat) induced immediate and significant hypotension and bradycardia. These responses were unaffected by intravenous (i.v.) methylatropine (1 mg/kg) or bilateral vagotomy, while they were prevented by i.t. lidocaine (25 microl at 1%) or i.v. hexamethonium (30 mg/kg). However, i.v. atenolol (1.5 mg/kg) suppressed the apomorphine-induced bradycardia without affecting the hypotension in either intact or bivagotomized rats. Bilateral adrenalectomy had no effect upon both maximal hypotensive and bradycardic responses to apomorphine (48 microg/rat at the T9-T10 level). These results suggest that hypotensive and bradycardic responses to i.t. apomorphine are due to an action in the spinal cord, presumably on sympathetic preganglionic neurons. These responses are dissociated and seem to result from withdrawal of sympathetic outflow to the vasculature and to the heart, respectively.

Topics: Adrenalectomy; Adrenergic beta-Antagonists; Animals; Anti-Arrhythmia Agents; Apomorphine; Atenolol; Atropine Derivatives; Blood Pressure; Bradycardia; Dopamine Agents; Ganglionic Blockers; Heart Rate; Hexamethonium; Hypotension; Injections, Spinal; Lidocaine; Male; Parasympatholytics; Rats; Rats, Wistar; Receptors, Dopamine; Spinal Cord; Sympatholytics; Time Factors; Vagotomy

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

In urethane-anesthetized rats, sodium L-glutamate (Glu) microinjection into the anteroventral third ventricle region (AV3V) induced a depressor response, but the heart rate remained unchanged, whereas Glu injection into its surrounding areas or normal saline injection into the AV3V had no effect on the arterial pressure and heart rate. Bilateral preinjection of procaine or atriopeptin III antiserum into the nucleus paraventricularis (NPV) and methyl atropine (IV) markedly attenuated the AV3V depressor response, but the hypotensive response was not significantly affected by phentolamine or propranolol (IV), indicating that atriopeptin in the NPV mediates the AV3V depressor response, and excitation of the cardiac vagus is also involved in this response.

Topics: Animals; Atrial Natriuretic Factor; Atropine Derivatives; Blood Pressure; Cerebral Ventricles; Drug Interactions; Hypotension; Hypothalamus; Injections, Intraventricular; Male; Paraventricular Hypothalamic Nucleus; Peptide Fragments; Phentolamine; Procaine; Propranolol; Rats; Rats, Wistar; Sodium Glutamate

Vasodepressor reactions were induced in 27 rats by a combination of inferior vena caval occlusion and an infusion of isoproterenol. A vasodepressor reaction was defined as paradoxical heart rate slowing during inferior vena caval occlusion. The R-R intervals were measured at 5-s intervals before, during, and after 60 s of inferior vena caval occlusion. The purpose of this study was to examine the role of the right and left vagus nerve and the right and left stellate ganglia in this reflex. Under control conditions inferior vena caval occlusion accelerated the rate (R-R, -15.9 +/- 0.9 ms). During an infusion of isoproterenol (0.5-1.0 micrograms.min-1), inferior vena caval occlusion produced paradoxical rate slowing, i.e., a vasodepressor reaction (R-R, +75.0 +/- 2.2 ms). The vasodepressor reaction was examined during inferior vena caval occlusion and isoproterenol under the following additional states: atropine methyl bromide or right vagotomy did not alter the reaction; left vagotomy eliminated the reaction; and right or left stellectomy greatly reduced the vasodepressor reaction. We conclude the following: (1) left vagal afferents mediate the vasodepressor reaction; (2) cardiac sympathetic fibers participate in the vasodepressor reaction by withdrawing efferent tone through the right stellate ganglion, and by generating the afferent signal, which triggers the vasodepressor reaction through the left stellate ganglion.

Topics: Animals; Atropine Derivatives; Bradycardia; Disease Models, Animal; Heart; Heart Ventricles; Hypotension; Isoproterenol; Male; Muscle Contraction; Muscle, Smooth, Vascular; Myocardial Contraction; Neurons, Afferent; Parasympatholytics; Rats; Rats, Wistar; Reflex; Stellate Ganglion; Syncope; Thrombophlebitis; Vagotomy; Vagus Nerve; Vena Cava, Inferior