methylatropine and Bradycardia

The crosstalk between the immune and the autonomic nervous system may impact the cardiovascular function. Toll-like receptors are components of the innate immune system and play developmental and physiological roles. Toll-like receptor 9 (TLR9) is involved in the pathogenesis of cardiovascular diseases, such as hypertension and heart failure. Since such diseases are commonly accompanied by autonomic imbalance and lower baroreflex sensitivity, we hypothesized that TLR9 modulates cardiac autonomic and baroreflex control of arterial pressure (AP). Toll-like receptor 9 knockout (TLR9 KO) and wild-type (WT) mice were implanted with catheters into carotid artery and jugular vein and allowed to recover for 3 days. After basal recording of AP, mice received methyl-atropine or propranolol. AP and pulse interval (PI) variability were evaluated in the time and frequency domain (spectral analysis), as well as by multiscale entropy. Spontaneous baroreflex was studied by sequence technique. Behavioral and cardiovascular responses to fear-conditioning stress were also evaluated. AP was similar between groups, but TLR9 KO mice exhibited lower basal heart rate (HR). AP variability was not different, but PI variability was increased in TLR9 KO mice. The total entropy was higher in TLR9 KO mice. Moreover, baroreflex function was found higher in TLR9 KO mice. Atropine-induced tachycardia was increased in TLR9 KO mice, whereas the propranolol-induced bradycardia was similar to WT mice. TLR9 KO mice exhibit increased behavioral and decreased tachycardia responses to fear-conditioning stress. In conclusion, our findings suggest that TLR9 may negatively modulate cardiac vagal tone and baroreflex in mice.

Topics: Animals; Arterial Pressure; Atropine Derivatives; Baroreflex; Behavior, Animal; Bradycardia; Cardiovascular System; Conditioning, Psychological; Disease Models, Animal; Fear; Heart Rate; Immunity, Innate; Male; Mice, Inbred C57BL; Mice, Knockout; Propranolol; Signal Transduction; Tachycardia; Time Factors; Toll-Like Receptor 9; Vagus Nerve

The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation.

Topics: Animals; Antihypertensive Agents; Atropine Derivatives; Autonomic Nervous System; Body Weight; Bradycardia; Female; Hemodynamics; Hypertension; Menopause; Ovariectomy; Parasympatholytics; Physical Conditioning, Animal; Propranolol; Rats, Inbred SHR; Rats, Wistar; Reproducibility of Results; Resistance Training; Time Factors

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

We have observed that in chloralose-anesthetized animals, gastric distension (GD) typically increases blood pressure (BP) under normoxic normocapnic conditions. However, we recently noted repeatable decreases in BP and heart rate (HR) in hypercapnic-acidotic rats in response to GD. The neural pathways, central processing, and autonomic effector mechanisms involved in this cardiovascular reflex response are unknown. We hypothesized that GD-induced decrease in BP and HR reflex responses are mediated during both withdrawal of sympathetic tone and increased parasympathetic activity, involving the rostral (rVLM) and caudal ventrolateral medulla (cVLM) and the nucleus ambiguus (NA). Rats anesthetized with ketamine and xylazine or α-chloralose were ventilated and monitored for HR and BP changes. The extent of cardiovascular inhibition was related to the extent of hypercapnia and acidosis. Repeated GD with both anesthetics induced consistent falls in BP and HR. The hemodynamic inhibitory response was reduced after blockade of the celiac ganglia or the intraabdominal vagal nerves with lidocaine, suggesting that the decreased BP and HR responses were mediated by both sympathetic and parasympathetic afferents. Blockade of the NA decreased the bradycardia response. Microinjection of kainic acid into the cVLM reduced the inhibitory BP response, whereas depolarization blockade of the rVLM decreased both BP and HR inhibitory responses. Blockade of GABA(A) receptors in the rVLM also reduced the BP and HR reflex responses. Atropine methyl bromide completely blocked the reflex bradycardia, and atenolol blocked the negative chronotropic response. Finally, α(1)-adrenergic blockade with prazosin reversed the depressor. Thus, in the setting of hypercapnic-acidosis, a sympathoinhibitory cardiovascular response is mediated, in part, by splanchnic nerves and is processed through the rVLM and cVLM. Additionally, a vagal excitatory reflex, which involves the NA, facilitates the GD-induced decreases in BP and HR responses. Efferent chronotropic responses involve both increased parasympathetic and reduced sympathetic activity, whereas the decrease in BP is mediated by reduced α-adrenergic tone.

Topics: Acidosis; Adrenergic alpha-1 Receptor Antagonists; Anesthetics; Animals; Atenolol; Atropine Derivatives; Blood Pressure; Bradycardia; Gastric Dilatation; Heart Rate; Hypercapnia; Kainic Acid; Male; Medulla Oblongata; Parasympathetic Nervous System; Parasympatholytics; Prazosin; Rats; Rats, Sprague-Dawley; Receptors, GABA-A; Reflex; Sympathetic Nervous System; Sympatholytics

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

The parasubthalamic nucleus (PSTN) projects extensively to the nucleus of the solitary tract (NTS); however, the function of PSTN in cardiovascular regulation is unknown. Experiments were done in alpha-chloralose anesthetized, paralyzed, and artificially ventilated rats to investigate the effect of glutamate (10 nl, 0.25 M) activation of PSTN neurons on mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). Glutamate stimulation of PSTN elicited depressor (-20.4 +/- 0.7 mmHg) and bradycardia (-26.0 +/- 1.0 beats/min) responses and decreases in RSNA (67 +/- 17%). Administration (intravenous) of atropine methyl bromide attenuated the bradycardia response (46%), but had no effect on the MAP response. Subsequent intravenous administration of hexamethonium bromide blocked both the remaining bradycardia and depressor responses. Bilateral microinjection of the synaptic blocker CoCl(2) into the caudal NTS region attenuated the PSTN depressor and bradycardia responses by 92% and 94%, respectively. Additionally, prior glutamate activation of neurons in the ipsilateral NTS did not alter the magnitude of the MAP response to stimulation of PSTN, but potentiated HR response by 35%. Finally, PSTN stimulation increased the magnitude of the reflex bradycardia to activation of arterial baroreceptors. These data indicate that activation of neurons in the PSTN elicits a decrease in MAP due to sympathoinhibition and a cardiac slowing that involves both vagal excitation and sympathoinhibition. In addition, these data suggest that the PSTN depressor effects on circulation are mediated in part through activation of NTS neurons involved in baroreflex function.

Topics: Animals; Atropine Derivatives; Baroreflex; Blood Pressure; Bradycardia; Cobalt; Glutamic Acid; Heart Rate; Hexamethonium; Injections, Intravenous; Kidney; Male; Medulla Oblongata; Microinjections; Muscarinic Antagonists; Neural Inhibition; Neural Pathways; Nicotinic Antagonists; Rats; Rats, Wistar; Solitary Nucleus; Sympathetic Nervous System; Thalamic Nuclei

We have previously shown that activation of P2X purinoceptors in the subpostremal nucleus tractus solitarius (NTS) produces a rapid bradycardia and hypotension. This bradycardia could occur via sympathetic withdrawal, parasympathetic activation, or a combination of both mechanisms. Thus we investigated the relative roles of parasympathetic activation and sympathetic withdrawal in mediating this bradycardia in chloralose-urethane anesthetized male Sprague-Dawley rats. Microinjections of the selective P2X purinoceptor agonist alpha,beta-methylene ATP (25 pmol/50 nl and 100 pmol/50 nl) were made into the subpostremal NTS in control animals, after atenolol (2 mg/kg i.v.), a beta1-selective antagonist, and after atropine methyl bromide (2 mg/kg i.v.), a muscarinic receptor antagonist. The bradycardia observed with activation of P2X receptors at the low dose of the agonist is mediated almost entirely by sympathetic withdrawal. After beta1-adrenergic blockade, the bradycardia was reduced to just -5.1 +/- 0.5 versus -28.8 +/- 5.1 beats/min in intact animals. Muscarinic blockade did not produce any significant change in the bradycardic response at the low dose. At the high dose, both beta1-adrenergic blockade and muscarinic blockade attenuated the bradycardia similarly, -37.4 +/- 6.4 and -40.6 +/- 3.7 beats/min, respectively, compared with -88.0 +/- 11 beats/min in control animals. Double blockade of both beta1-adrenergic and muscarinic receptors virtually abolished the response (-2.5 +/- 0.8 beats/min). We conclude that the relative contributions of parasympathetic activation and sympathetic withdrawal are dependent on the extent of P2X receptor activation.

Topics: Adenosine Triphosphate; Adrenergic beta-Antagonists; Animals; Atenolol; Atropine Derivatives; Bradycardia; Injections, Intravenous; Male; Microinjections; Muscarinic Antagonists; Parasympathetic Nervous System; Purinergic P2 Receptor Agonists; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2; Receptors, Purinergic P2X; Solitary Nucleus; 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

Previous studies of the effects of electrical vagus stimulation on experimental seizures were without suitable controls or statistical validation, and ignored the potential role of vagally-induced hemodynamic depression on seizure expression. This study addresses these limitations. The effects of periodic left vagus nerve stimulation (LVNS) on chemically-induced seizures in rats were compared with control groups receiving no stimulation (NoS), left sciatic nerve stimulation (LSNS) and LVNS after pretreatment with methyl atropine (MA-LVNS). Stimulation followed a 30 s on-120 s off cycle over 130 min. Seizures were scored visually and the temporal variation of their probability P(s) across the stimulation cycle was measured statistically. P(s) was significantly different (P<0.01) for all groups: LSNS had the highest and MA-LVNS the lowest seizure probability; LVNS and NoS had intermediate values. While LVNS blocked seizures, it also precipitated them, explaining why its anti-seizure effect was only slightly greater than NoS. Neither LVNS nor MA-LVNS induced changes in cortical rhythms ('activation') associated with decreased P(s), unlike LSNS which increased cortical rhythm synchrony and with it, P(s). LVNS alone induced marked bradycardia and moderate hypoxemia. In conclusion, cranial and peripheral nerve stimulation have complex, time-varying effects on cerebral excitability: low frequency LSNS facilitated seizures, while LVNS both suppressed and facilitated them. The anti-seizure effect of LVNS was small and may have, in part, been due to a hemodynamically-induced deficit in energy substrates. The effects of MA-LVNS on seizure duration and P(s) raise the possibility that, in the absence of hemodynamic depression, stimulation of this nerve does not have a strong anti-seizure effect.

Topics: Animals; Atropine Derivatives; Bradycardia; Cerebral Cortex; Cerebrovascular Circulation; Cortical Synchronization; Electric Stimulation Therapy; Male; Models, Neurological; Movement Disorders; Neural Conduction; Parasympatholytics; Rats; Rats, Sprague-Dawley; Reaction Time; Respiratory Physiological Phenomena; Sciatic Nerve; Seizures; Time Factors; Vagus Nerve

Based on the inactive metabolite approach, three different classes of soft drugs were designed and synthesized. Their cardiovascular effects and duration of actions were studied in anesthetized male Sprague-Dawley rats compared to the traditional drugs. During the experiments ECG (leads II, aVF) and beat-to-beat blood pressure (BP) from the left carotid artery were recorded (except during the anticholinergic studies). The soft anticholinergic methoxycarbonylphenylcyclopentyl-N,N-dimethyltropinium methyl sulfate was as potent as atropine in the prevention of carbachol induced bradycardia; however, its action only lasted up to 15-30 min, compared to 2 h of that of atropine. In the isoproterenol-induced tachycardia model, while bufuralol at an i.v. dose of 3.8 mumol/kg (1 mg/kg) diminished heart rate (HR) for at least 2 h, the effects of the soft drugs lasted for only 30-40 min at equimolar doses. The methyl-, ethyl-, isopropyl-, and tert-butyl ester-analogs of the carboxylic acid metabolite of bufuralol showed the highest beta-blocking potencies (i.e., 30-50% of that of bufuralol). When these compounds were infused for 10 min at doses ranging from 2-4 mumol/kg/min, they caused a 20-40% decrease in HR and a 30-40% reduction in mean arterial pressure (MAP). These effects were similar to those elicited by esmolol at a dose of 20 mumol/kg/min in respect of the kinetics and in the extent of the reductions in heart rate and MAP. The isopropyl-, the sec-butyl-, and the neopentyl-esters of the acidic metabolite of amiodarone, with plasma hydrolytic half-lives of 60, 240 and 300 min, were tested in the benzene/adrenaline induced ventricular tachycardia (VT) model of the rat. All drugs were administered at a dose of 5 mumol/kg i.v. bolus immediately followed by an infusion at 15 mumol/kg/h for 2 h. It was found, that amiodarone resulted a complete suppression of VTs at 30 min after the start of drug administration, but its effect lasted up to the total course of the experiment (up to 180 min). On the contrary, both the sec-butyl and the isopropyl-analog resulted in complete suppression of VTs already during the first benzene/adrenaline challenge after drug administration (i.e., at 5 min). However, their effects disappeared between 15 and 30 min after discontinuation of the drug infusions in accordance with the enzymatic inactivation (ester hydrolysis) of these soft drugs. All these three classes of soft cardioactive drugs are good examples for highly potent but short

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Anti-Arrhythmia Agents; Atropine Derivatives; Biotransformation; Blood Pressure; Bradycardia; Carbachol; Cardiovascular Agents; Drug Design; Ethanolamines; Heart Rate; Isoproterenol; Male; Muscarinic Agonists; Prodrugs; Rats; Rats, Sprague-Dawley; Tropanes

The presence of insulin and insulin binding sites in the central nervous system and the demonstration that central insulin has an effect on cardiovascular function has led to the hypothesis that insulin may play a role in mediating the baroreceptor reflex. To investigate this possibility, insulin was microinjected into depressor sites in the nucleus tractus solitarius (NTS), the first central synapse of the baroreceptor reflex, of urethane anesthetized rats. Microinjection of insulin into the NTS (110 nL of 1, 10 and 100 IU/mL) did not change mean arterial pressure (MAP) or heart rate (HR). However, insulin microinjection attenuated phenylephrine-elicited reflex bradycardia and depressor responses elicited by glutamate (GLU). The attenuation of GLU-elicited depressor responses was time-dependent for MAP changes and time and concentration-dependent for HR changes (p < 0.05). Insulin-like growth factor-1 microinjection into the NTS also attenuated GLU-elicited decreases in MAP (p < 0.05) but not HR. The effect of insulin on GLU-elicited responses was inhibited after peripheral adrenergic blockade by nadolol (1.0 mg/kg i.v.) but not after cholinergic blockade by methyl-atropine (2.0 mg/kg i.v.). These results demonstrate that insulin inhibits baroreceptor reflex responses in the NTS likely through an influence on the effects of excitatory amino acid neurotransmitters on the activity of NTS neurons involved in sympathetic control of the cardiovascular system.

Topics: Anesthetics, Intravenous; Animals; Atropine Derivatives; Baroreflex; Bradycardia; Cardiovascular System; Dose-Response Relationship, Drug; Glutamic Acid; Hypoglycemic Agents; Insulin; Insulin-Like Growth Factor I; Male; Microinjections; Nadolol; Parasympatholytics; Phenylephrine; Rats; Rats, Wistar; Solitary Nucleus; Sympathetic Nervous System; Sympatholytics; Sympathomimetics; Urethane

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

The injection of neostigmine into the hippocampus of anesthetized rats increased the mean arterial blood pressure (17% of baseline after 60 min injection) and decreased the heart rate (24% of baseline after 60 min injection). These changes were blocked by the co-administration of methylatropine into the hippocampus. Intrahippocampal injection of neostigmine stimulated the secretion of epinephrine and norepinephrine. Adrenodemedullation did not suppress the increase in blood pressure and the decrease in heart rate. It is concluded that the stimulation of muscarinic cholinoceptive neurons in the hippocampus evokes a hypertensive response via an increase in sympathetic drive to the heart and peripheral vasculature, with bradycardia possibly mediated via the parasympathetic system.

Topics: Animals; Atropine Derivatives; Blood Pressure; Bradycardia; Epinephrine; Heart Rate; Hippocampus; Kinetics; Male; Neostigmine; Norepinephrine; Rats; Rats, Inbred Strains; Receptors, Cholinergic; Receptors, Muscarinic

The cardiovascular effects of centrally administered cholinomimetics were examined in conscious Long-Evans and Brattleboro rats. Carbachol (1 microgram/kg) or physostigmine (50 micrograms/kg) induced a long-lasting increase in blood pressure and a decrease in heart rate in Long-Evans rats whereas no bradycardia was observed in Brattleboro rats, and the pressor response was significantly less than that in Long-Evans rats. The cardiovascular responses to nicotine (30 micrograms/kg) in Brattleboro rats were not different from those in Long-Evans rats. Intravenous vasopressin antagonist, d(CH2)5Tyr(Me) arginine vasopressin, significantly attenuated the pressor response and eliminated the bradycardic response to carbachol in Long-Evans rats. However, the pressor response to carbachol in Brattleboro rats was still significantly less than that in Long-Evans rats treated with vasopressin antagonist. Intravenous phentolamine partially inhibited the pressor response to carbachol in Long-Evans rats and completely eliminated it in Brattleboro rats. Combined intravenous treatment with phentolamine and vasopressin antagonist completely eliminated the pressor response to carbachol in Long-Evans rats. Centrally administered methylatropine eliminated either the hypertensive or bradycardic response to carbachol in Long-Evans rats. These results indicate that the pressor and bradycardic response to carbachol or physostigmine is mediated by the central muscarinic receptor mechanism. Hypertensive response to intracerebroventricularly administered carbachol in normal rats is mediated both by an increase in central sympathetic outflow and in circulating vasopressin. The bradycardia seems to be mediated mainly by vasopressin.

Topics: Animals; Arginine Vasopressin; Atropine Derivatives; Autonomic Nervous System; Blood Pressure; Bradycardia; Carbachol; Cardiovascular Physiological Phenomena; Cardiovascular System; Deamino Arginine Vasopressin; Hypertension; Injections, Intraventricular; Male; Nicotine; Parasympatholytics; Phentolamine; Physostigmine; Rats; Rats, Brattleboro; Vasopressins

Neuropeptide Y (NPY) is contained in and coreleased with norepinephrine (NE) from sympathetic nerves innervating vascular and cardiac tissues. The effects of NPY infusion on systemic hemodynamics and cardiac performance were compared with those of NE in conscious and pentobarbital sodium-anesthetized rats. A 10-min infusion of NPY (2 nmol.kg-1.min-1) decreased cardiac index (CI) 20% and stroke volume index (SVI) 9% with increases of 20% in mean arterial pressure (MAP) and 48% in total peripheral resistance (TPR). Conversely, NE (1.0 microgram.kg-1.min-1) increased SVI 14%, MAP 29%, and TRP 26%, with no change in CI. Heart rates decreased similarly (approximately 60 beats/min) but only NE-induced bradycardia was reversible by methylatropine nitrate. In anesthetized rats NPY (0.1 nmol.kg-1.min-1) increased left ventricular end-diastolic pressure (LVEDP) 20 +/- 10 mmHg (means +/- SD, n = 7) and decreased dP/dt by 8 +/- 6%. NE (0.07 microgram.kg-1.min-1) produced an equivalent pressor response, however, dP/dt rose 22 +/- 10% whereas LVEDP increased significantly less than with NPY. Thus NPY is a potent vasoconstrictor exerting similar effects to NE on MAP and TPR but, unlike NE, possesses negative inotropic and chronotropic activity.

Topics: Animals; Atropine Derivatives; Blood Pressure; Bradycardia; Depression, Chemical; Heart Rate; Hemodynamics; Male; Neuropeptide Y; Norepinephrine; Rats; Rats, Inbred Strains; Vasoconstriction

The cardiovascular effects of centrally administered 5-hydroxytryptamine (5-HT) have been analysed in conscious normotensive and hypertensive rats. In conscious normotensive rats, 5-HT, (1-30 micrograms) administered intracerebroventricularly (i.c.v.) produced profound and immediate dose-related decreases in heart rate and small increases in blood pressure. The initial pressor responses were followed by secondary secondary depressor responses at high doses of 5-HT. Similar effects were produced by 5-HT i.c.v. in conscious DOCA-salt and spontaneously hypertensive rats, although the magnitude of the pressor responses was substantially greater in hypertensive than normotensive rats. Pretreatment with either N-methylatropine or atenolol intra-arterially reduced the 5-HT-induced bradycardia in normotensive rats; the reduction was enhanced when both antagonists were given in combination. The 5-HT2 antagonist, cyproheptadine (10 micrograms i.c.v.) increased basal blood pressure and heart rate in normotensive rats. Subsequent administration of 5-HT i.c.v. produced biphasic effects on heart rate consisting of an initial tachycardia followed by a marked bradycardia. Methysergide (10 micrograms i.c.v.) pretreatment did not alter resting heart rate, but attenuated the 5-HT induced bradycardia. A higher dose of methysergide, (30 micrograms i.c.v.), decreased resting blood pressure and heart rate. This study has demonstrated, therefore, that the 5-HT induced bradycardia is produced by not only a centrally mediated decrease in sympathetic tone, but also an increase in vagal drive to the heart. The bradycardia is antagonised by centrally administered methysergide, but not by cyproheptadine, which suggests that it is probably mediated through a '5-HT1-like' receptor mechanism.

Topics: Animals; Atenolol; Atropine Derivatives; Blood Pressure; Bradycardia; Drug Interactions; Heart; Heart Rate; Hypertension; Injections, Intravenous; Male; Methysergide; Rats; Serotonin; Serotonin Antagonists