RESUMO
Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.
Assuntos
Animais , Masculino , Fluoxetina/administração & dosagem , Rim/efeitos dos fármacos , Paroxetina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Sertralina/administração & dosagem , Sistema Nervoso Simpático/efeitos dos fármacos , Antidepressivos/administração & dosagem , Antidepressivos/farmacologia , Pressão Arterial/efeitos dos fármacos , Barorreflexo/efeitos dos fármacos , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Fluoxetina/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Rim/inervação , Rim/cirurgia , Paroxetina/farmacologia , Ratos Wistar , Taxa Respiratória/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Sertralina/farmacologia , Sinais Vitais/efeitos dos fármacosRESUMO
The objective of the present study was to determine the antihyperalgesic effect of sertraline, measured indirectly by the changes of sciatic afferent nerve activity, and its effects on cardiorespiratory parameters, using the model of formalin-induced inflammatory nociception in anesthetized rats. Serum serotonin (5-HT) levels were measured in order to test their correlation with the analgesic effect. Male Wistar rats (250-300 g) were divided into 4 groups (N = 8/per group): sertraline-treated group (Sert + Saline (Sal) and Sert + Formalin (Form); 3 mg·kg-1·day-1, ip, for 7 days) and saline-treated group (Sal + Sal and Sal + Form). The rats were injected with 5 percent (50 µL) formalin or saline into the right hind paw. Sciatic nerve activity was recorded using a silver electrode connected to a NeuroLog apparatus, and cardiopulmonary parameters (mean arterial pressure, heart rate and respiratory frequency), assessed after arterial cannulation and tracheotomy, were monitored using a Data Acquisition System. Blood samples were collected from the animals and serum 5-HT levels were determined by ELISA. Formalin injection induced the following changes: sciatic afferent nerve activity (+50.8 ± 14.7 percent), mean arterial pressure (+1.4 ± 3 mmHg), heart rate (+13 ± 6.8 bpm), respiratory frequency (+4.6 ± 5 cpm) and serum 5-HT increased to 1162 ± 124.6 ng/mL. Treatment with sertraline significantly reduced all these parameters (respectively: +19.8 ± 6.9 percent, -3.3 ± 2 mmHg, -13.1 ± 10.8 bpm, -9.8 ± 5.7 cpm) and serum 5-HT level dropped to 634 ± 69 ng/mL (P < 0.05). These results suggest that sertraline plays an analgesic role in formalin-induced nociception probably through a serotonergic mechanism.
Assuntos
Animais , Masculino , Ratos , Formaldeído/antagonistas & inibidores , Nociceptividade/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Sertralina/farmacologia , Pressão Arterial/efeitos dos fármacos , Formaldeído/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Medição da Dor/efeitos dos fármacos , Ratos Wistar , Taxa Respiratória/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Serotonina/sangueRESUMO
Activation of 5-hydroxytryptamine (5-HT) 5-HT1A, 5-HT2C, 5-HT3, and 5-HT7 receptors modulates the excitability of cardiac vagal motoneurones, but the precise role of 5-HT2A/2B receptors in these phenomena is unclear. We report here the effects of intracisternal (ic) administration of selective 5-HT2A/2B antagonists on the vagal bradycardia elicited by activation of the von Bezold-Jarisch reflex with phenylbiguanide. The experiments were performed on urethane-anesthetized male Wistar rats (250-270 g, N = 7-9 per group). The animals were placed in a stereotaxic frame and their atlanto-occipital membrane was exposed to allow ic injections. The rats received atenolol (1 mg/kg, iv) to block the sympathetic component of the reflex bradycardia; 20-min later, the cardiopulmonary reflex was induced with phenylbiguanide (15 µg/kg, iv) injected at 15-min intervals until 3 similar bradycardias were obtained. Ten minutes after the last pre-drug bradycardia, R-96544 (a 5-HT2A antagonist; 0.1 µmol/kg), SB-204741 (a 5-HT2B antagonist; 0.1 µmol/kg) or vehicle was injected ic. The subsequent iv injections of phenylbiguanide were administered 5, 20, 35, and 50 min after the ic injection. The selective 5-HT2A receptor antagonism attenuated the vagal bradycardia and hypotension, with maximal effect at 35 min after the antagonist (pre-drug = -200 ± 11 bpm and -42 ± 3 mmHg; at 35 min = -84 ± 10 bpm and -33 ± 2 mmHg; P < 0.05). Neither the 5-HT2B receptor antagonists nor the vehicle changed the reflex. These data suggest that central 5-HT2A receptors modulate the central pathways of the parasympathetic component of the von Bezold-Jarisch reflex.
Assuntos
Animais , Masculino , Ratos , Bradicardia/fisiopatologia , /fisiologia , Reflexo/efeitos dos fármacos , Nervo Vago/efeitos dos fármacos , Analgésicos/farmacologia , Atenolol/farmacologia , Biguanidas/farmacologia , Bradicardia/induzido quimicamente , Ratos Wistar , Reflexo/efeitos da radiação , Agonistas do Receptor de Serotonina/farmacologia , Nervo Vago/fisiopatologiaRESUMO
We determined the effects of helium-neon (He-Ne) laser irradiation on wound healing dynamics in mice treated with steroidal and non-steroidal anti-inflammatory agents. Male albino mice, 28-32 g, were randomized into 6 groups of 6 animals each: control (C), He-Ne laser (L), dexamethasone (D), D + L, celecoxib (X), and X + L. D and X were injected im at doses of 5 and 22 mg/kg, respectively, 24 h before the experiment. A 1-cm long surgical wound was made with a scalpel on the abdomens of the mice. Animals from groups L, D + L and X + L were exposed to 4 J (cm²)-1 day-1 of He-Ne laser for 12 s and were sacrificed on days 1, 2, or 3 after the procedure, when skin samples were taken for histological examination. A significant increase of collagen synthesis was observed in group L compared with C (168 ± 20 vs 63 ± 8 mm²). The basal cellularity values on day 1 were: C = 763 ± 47, L = 1116 ± 85, D = 376 ± 24, D + L = 698 ± 31, X = 453 ± 29, X + L = 639 ± 32 U/mm². These data show that application of L increases while D and X decrease the inflammatory cellularity compared with C. They also show that L restores the diminished cellularity induced by the anti-inflammatory drugs. We suggest that He-Ne laser promotes collagen formation and restores the baseline cellularity after pharmacological inhibition, indicating new perspectives for laser therapy aiming to increase the healing process when anti-inflammatory drugs are used.
Assuntos
Animais , Masculino , Camundongos , Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Terapia com Luz de Baixa Intensidade , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Cicatrização/efeitos da radiação , Hélio/uso terapêutico , Neônio/uso terapêutico , Cicatrização/efeitos dos fármacosRESUMO
Epidemiological and clinical evidence suggests that a judicious diet, regular physical activity and blood pressure (BP) monitoring must start in early childhood to minimize the impact of modifiable cardiovascular risk factors. This study was designed to evaluate BP and metabolic parameters of schoolchildren from Vitória, Espírito Santo State, Brazil, and correlate them with cardiovascular risk factors. The study was conducted on 380 students aged 10-14 years (177 boys, 203 girls) enrolled in public schools. Baseline measurements included body mass index, BP and heart rate. The students were submitted to exercise spirometry on a treadmill. VO2max was obtained from exercise testing to voluntary exhaustion. Fasting serum total cholesterol (TC), LDL-C, HDL-C, triglycerides (TG), and glucose were measured. Nine point nine percent of the boys and 11.7 percent of the girls were hypertensive or had pre-hypertensive levels. There was no significant correlation between VO2max and TC, LDL-C, or TG in prepubertal children, but a slight negative correlation was detected in post-pubertal boys for HDL-C and TG. In addition, children with hypertension (3.4 percent) or pre-hypertensive levels (6.6 percent) also had comorbidity for overweight and blood lipid abnormalities (14 percent for triglycerides, 44.7 percent for TC, 25.9 percent for LDL-C, 52 percent for low HDL-C). The present study shows for the first time high correlations between prehypertensive blood pressure levels and the cardiovascular risk factors high TC, high LDL-C, low HDL-C in schoolchildren. These are important for the formulation of public health policies and strategies.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Frequência Cardíaca/fisiologia , Lipídeos/sangue , Índice de Massa Corporal , Brasil/epidemiologia , Estudos Transversais , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Teste de Esforço , Glucose/análise , Prevalência , Fatores de Risco , EspirometriaRESUMO
Depression found in Parkinson disease (PD) usually responds to selective serotonin reuptake inhibitors (SSRIs). Drugs that modify experimental neuroleptic catalepsy (NC) might affect extrapyramidal symptoms in PD. Therefore, the effects of SSRIs on NC were tested in mice, 26-36 g, separated by sex. Catalepsy was induced with haloperidol (H; 1 mg/kg, ip) and measured at 30-min intervals using a bar test. An SSRI (sertraline, ST; paroxetine, PX; fluoxetine) or vehicle (C) was injected ip 30 min before H. Dunnett's test was used for comparison of means. ST (1-5 mg/kg) or PX (1-5 mg/kg) attenuated NC, with a similar inhibition found in both sexes (5 mg/kg, 180 min: ST - males: 124 ± 10 vs 714 ± 15 s in C; females: 116 ± 10 vs 718 ± 6 s in C; PX - males: 106 ± 10 vs 714 ± 14 s in C; females: 102 ± 10 vs 715 ± 14 s in C). At 0.3 mg/kg, neither of these drugs affected NC. Fluoxetine (1-25 mg/kg) also inhibited catalepsy, although the effect was not dose-dependent; no differences were observed between males and females (5 mg/kg, 180 min: males, 185 ± 14 vs 712 ± 14 s in C; females, 169 ± 10 vs 710 ± 19 s in C). For these SSRIs, maximal inhibition of NC was obtained with 5 mg/kg, 180 min after H. These results are consistent with the hypothesis that serotonergic mechanisms modulate nigrostriatal transmission, and suggest that SSRIs are possibly safe in depressive PD patients.
Assuntos
Animais , Masculino , Feminino , Camundongos , Catalepsia/tratamento farmacológico , Fluoxetina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Paroxetina/farmacologia , Sertralina/farmacologia , Antidiscinéticos , Catalepsia/induzido quimicamente , Modelos Animais de Doenças , Haloperidol , Fatores Sexuais , Fatores de TempoRESUMO
The dorsal (DRN) and median (MRN) raphe nuclei are important sources of serotonergic innervation to the forebrain, projecting to sites involved in cardiovascular regulation. These nuclei have been mapped using electrical stimulation, which has the limitation of stimulating fibers of passage. The present study maps these areas with chemical stimulation, investigating their influence on cardiorespiratory parameters. Urethane-anesthetized (1.2 g/kg, iv) male Wistar rats (280-300 g) were instrumented for pulsatile and mean blood pressure (MBP), heart rate, renal nerve activity, and respiratory frequency recordings. Microinjections of L-glutamate (0.18 M, 50-100 nl with 1 percent Pontamine Sky Blue) were performed within the DRN or the MRN with glass micropipettes. At the end of the experiments the sites of microinjection were identified. The majority of sites within the MRN (86.1 percent) and DRN (85.4 percent) evoked pressor responses when stimulated (DRN: deltaMBP = +14.7 ± 1.2; MRN: deltaMBP = +13.6 ± 1.3 mmHg). The changes in renal nerve activity and respiratory rate caused by L-glutamate were +45 ± 11 and +42 ± 9 percent (DRN; P < 0.05 percent), +40 ± 10 and +29 ± 7 percent (MRN, P < 0.05), respectively. No significant changes were observed in saline-microinjected animals. This study shows that: a) the blood pressure increases previously observed by electrical stimulation within the raphe are due to activation of local neurons, b) this pressor effect is due to sympathoexcitation because the stimulation increased renal sympathetic activity but did not produce tachycardia, and c) the stimulation of cell bodies in these nuclei also increases the respiratory rate.
Assuntos
Animais , Masculino , Ratos , Ácido Glutâmico/farmacologia , Mapeamento Encefálico , Neurônios/efeitos dos fármacos , Núcleo Mediodorsal do Tálamo/fisiologia , Núcleos da Rafe/fisiologia , Estimulação Elétrica , Frequência Cardíaca/fisiologia , Mecânica Respiratória/fisiologia , Núcleo Mediodorsal do Tálamo/citologia , Núcleos da Rafe/citologia , Pressão Arterial/fisiologia , Ratos WistarRESUMO
The two-kidney, one-clip renovascular (2K1C) hypertension model is characterized by a reduction in renal flow on the clipped artery that activates the renin-angiotensin system. Endothelium dysfunction, including diminished nitric oxide production, is also believed to play a role in the pathophysiology of this model. Some studies have shown an effect of L-arginine (L-Arg, a nitric oxide precursor) on hypertension. In the present study we determined the ability of L-Arg (7 days of treatment) to reduce blood pressure and alter renal excretions of water, Na+ and K+ in a model of 2K1C-induced hypertension. Under ether anesthesia, male Wistar rats (150-170 g) had a silver clip (0.20 mm) placed around the left renal artery to produce the 2K1C renovascular hypertension model. In the experimental group, the drinking water was replaced with an L-Arg solution (10 mg/ml; average intake of 300 mg/day) from the 7th to the 14th day after surgery. Sham-operated rats were used as controls. At the end of the treatment period, mean blood pressure was measured in conscious animals. The animals were then killed and the kidneys were removed and weighed. There was a significant reduction of mean blood pressure in the L-Arg-treated group when compared to control (129 ± 7 vs 168 ± 6 mmHg, N = 8-10 per group; P<0.05). Concomitantly, a significant enhancement of water and Na+ excretion was observed in the 2K1C L-Arg-treated group when compared to control (water: 13.0 ± 0.7 vs 9.2 ± 0.5 ml/day, P<0.01; Na+: 1.1 ± 0.05 vs 0.8 ± 0.05 mEq/day, respectively, P<0.01). These results show that orally administered L-Arg acts on the kidney, possibly inducing changes in renal hemodynamics or tubular transport due to an increase in nitric oxide formation
Assuntos
Animais , Masculino , Ratos , Arginina , Pressão Sanguínea , Hipertensão Renovascular , Sódio , Modelos Animais de Doenças , Diurese , Natriurese , Ratos WistarRESUMO
It has been suggested that nigrostriatal dopaminergic transmission is modulated by nitric oxide (NO). Since there is evidence that gonadal hormones can affect extrapyramidal motor behavior in mammals, we investigated the effects of isosorbide dinitrate (ISD), linsidomine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP), three pharmacologically different NO donors, on neuroleptic-induced catalepsy in 60- to 80-day-old male and female albino mice. Catalepsy was induced with haloperidol (1 mg/kg, ip) and measured at 30-min intervals by means of a bar test. Drugs (or appropriate vehicle) were injected ip 30 min before haloperidol, with each animal being used only once. ISD (5, 20 and 50 mg/kg) caused a dose-dependent inhibition of catalepsy in male mice (maximal effect 120 min after haloperidol: 64 percent inhibition). In the females only at the highest dose of ISD was an attenuation of catalepsy observed, which was mild and short lasting. SIN-1 (10 and 50 mg/kg) did not significantly affect catalepsy in female mice, while a significant attenuation was observed in males at the dose of 50 mg/kg (maximal inhibition: 60 percent). SNAP (20 mg/kg) significantly attenuated catalepsy in males 120 min after haloperidol (44 percent inhibition), but had no significant effect on females. These results basically agree with literature data showing that NO facilitates central dopaminergic transmission, although the mechanisms are not fully understood. They also reveal the existence of gender-related differences in this nitrergic modulation in mice, with females being less affected than males
Assuntos
Animais , Masculino , Feminino , Camundongos , Catalepsia , Doadores de Óxido Nítrico , Análise de Variância , Antipsicóticos , Catalepsia , Haloperidol , Dinitrato de Isossorbida , Molsidomina , S-Nitroso-N-Acetilpenicilamina/farmacologia , Fatores SexuaisRESUMO
Pressor responses elicited by stimulation of the nucleus raphe obscurus (NRO) depend on the integrity of the rostral ventrolateral medulla (RVLM). Therefore, to test the participation of excitatory amino acid (EAA) receptors in the cardiovascular responses evoked by NRO stimulation (1 ms, 100 Hz, 40-70 æA, for 10 s), the EAA antagonist kynurenic acid (Kyn) was microinjected at different sites in the ventrolateral medullar surface (2.7 nmol/200 nl) of male Wistar rats (270-320 g, N = 39) and NRO stimulation was repeated. The effects of NRO stimulation were: hypertension (deltaMAP = +43 ± 1 mmHg, P<0.01), bradycardia (deltaHR = -30 ± 7 bpm, P<0.01) and apnea. Bilateral microinjection of Kyn into the RVLM, which did not change baseline parameters, almost abolished the bradycardia induced by NRO stimulation (deltaHR = -61 ± 3 before vs -2 ± 3 bpm after Kyn, P<0.01, N = 7). Unilateral microinjection of Kyn into the CVLM did not change baseline parameters or reduce the pressor response to NRO stimulation (deltaMAP = +46 ± 5 before vs +48 ± 5 mmHg after Kyn, N = 6). Kyn bilaterally microinjected into the caudal pressor area reduced blood pressure and heart rate and almost abolished the pressor response to NRO stimulation (deltaMAP = +46 ± 4 mmHg before vs +4 ± 2 mmHg after Kyn, P<0.01, N = 7). These results indicate that EAA receptors on the medullary ventrolateral surface play a role in the modulation of the cardiovascular responses induced by NRO stimulation, and also suggest that the RVLM participates in the modulation of heart rate responses and that the caudal pressor area modulates the pressor response following NRO stimulation
Assuntos
Animais , Masculino , Ratos , Pressão Sanguínea , Antagonistas de Aminoácidos Excitatórios , Frequência Cardíaca , Ácido Cinurênico , Bulbo , Estimulação Elétrica , Bulbo , Microinjeções , Núcleos da Rafe , Ratos WistarRESUMO
The role of the caudal pressor area (CPA) in the maintenance of vasomotor tonus in anesthetized and decerebrate animals has been clearly established. In conscious animals, however, the participation of CPA in the cardiovascular control remains to be fully elucidated. In the present study, unilateral L-glutamate (L-Glu) (10 and/or 20 nmol/70 nl) microinjection into CPA, in conscious male Wistar rats (250-280 g) caused a significant increase in mean arterial blood pressure (MAP; control: 112 + or - 1.9 mmHg; after 20 nmol L-Glu: 139 + or - 4.5 mmHg, N = 12, P<0.05) and respiratory rate (control: 81 + or - 3.5 breaths/min; after 10 nmol L-Glu: 92 + or - 3 breaths/min, P<0.05; after 20 nmol L-Glu: 104 + or - 5 breaths/min, N = 6, P<0.05). The subsequent anesthesia with urethane caused a significant increase in basal respiratory frequency (conscious: 81 + or - 3.5 breaths/min; under urethane: 107 + or - 1.3 breaths/min, N = 6, P<0.05). Anesthesia also significantly attenuated L-Glu-evoked pressor (conscious: deltaMAP = +27 mmHg; anesthetized: deltaMAP = +18 mmHg, P<0.05) and respiratory responses. These results suggest that glutamatergic receptors in the CPA are involved in cardiovascular and respiratory modulation in conscious rats
Assuntos
Animais , Masculino , Ratos , Anestésicos Intravenosos , Pressão Sanguínea , Estado de Consciência , Ácido Glutâmico , Bulbo , Respiração , Frequência Cardíaca , Microinjeções , Ratos Wistar , UretanaRESUMO
The medullary raphe nuclei are involved in central autonomic regulation. In all species investigated, electrical stimulation of the raphe nuclei causes cardiovascular responses, although, these changes vary between species. The present study was designed to investigate the participation of these nuclei in cardiovascular regulation in the guinea pig. We studied the effect on arterial blood pressure (BP) and heart rate (HR) of electrical stimulation (isolated cathodal square wave pulses for 10 s at 100 Hz, 40-100 muA and 1-ms pulse duration) within the medullary raphe nuclei in urethane-anesthetized (1.2g/kg, i.p.) guinea pigs (400-600g. either sex). Electrical stimulation of the same sites was performed on a group of paralyzed (Flaxedil®, 1 mg/kg, i.v.) and artificially ventilated animals. Stimulation sites were histologically defined and maps of the stimuli were obtained for the effect of electrical stimulation on arterial blood pressure. In another series of experiments, L-glutamate (0.2 M) was microinjected (75 to 150 nl) into the nucleus raphe obscurus. Electrical stimulation of the raphe nuclei produced predominantly pressor responses (delta= +15 to +100 mmHg: 43 percent of the stimulated sites). Hypotension (delta= -10 to -25 mmHg, 24 percent of the stimulated sites), biphasic responses (2 percent) or no change in BP (31 percent) were evoked from fewer stimulation sites. Pressor responses were also predominant in paralyzed animals (delta= +15 to +95 mmHg; 47 percent of the stimulates sites), and after microinjection of L-glutamate into the raphe obscurus (A= +20 to +45 mmHg). The present results demonstrate that in the guinea pig the stimulation of these nuclei evokes mainly pressor responses. These responses are similar to those obtained in the rat and hamster but opposite to those observed in the cat and rabbit.
Assuntos
Animais , Cobaias , Masculino , Feminino , Pressão Sanguínea , Estimulação Elétrica/efeitos adversos , Frequência Cardíaca , Núcleos da Rafe , Glutamatos/farmacologia , MicroinjeçõesRESUMO
Neuroleptic-induced catalepsy remains a useful method to study central dopaminergic function in rodents. Evidence obtained in several studies indicates that this phenomenon can be modified by cholinergic, histaminergic and serotonergic manipulation. Angiotensin II is a central neurotransmitter acting through AT1 and AT2 receptors. There are few data on the effect of angiotensinergic drugs on dopaminergic transmission. We investigated the effect of losartan, a nonpeptide antagonist of central and peripheral AT1 receptors, on neuroleptic-induced catalepsy. Adult male albino mice, 26-35 g, were used. Catalepsy was induced with haloperidol (H; l mg/kg, ip) and measured at 30-min intervals by means of a bar test. Losartan (10 or 100 ng/kg) or saline (control; 0.13 ml) was injected intraperitoneally 20 min before H, with each animal (7 per group) being used only once. Losartan (10 and 100 ng/kg) significantly (P<0.05) potentiated the cataleptic effect of H in comparison to the control group (e.g. 264 ñ 26 and 299 ñ 68 sec, respectively, vs 89 ñ 24 sec for the control group, 90 min after H). No differences were demonstrable 120, 150 or 180 min after H. Considering the high selectivity and the pharmacokinetic properties of losartan, these data suggest that central angiotensin AT1 receptors play a role in neuroleptic-induced catalepsy. However, further studies are necessary to confirm this hypothesis and to clarify the mechanism(s) involved in this process.
Assuntos
Camundongos , Animais , Masculino , Compostos de Bifenilo/uso terapêutico , Catalepsia/tratamento farmacológico , Imidazóis/uso terapêutico , Receptores de Angiotensina/antagonistas & inibidores , Tetrazóis/uso terapêutico , Antipsicóticos/administração & dosagem , Camundongos EndogâmicosRESUMO
Transient vagal bradycardia occuring during coronary arteriography (CA) immediately following intracoronary injection of ionic contrast medium is believed to be a component of the von Bezold-Jarisch reflex (BJ). Data obtained from experimental animals using buspirone (BSP) and other 5-HT1A receptor ligands suggest that these serotonergic receptors modulate the excitability of cardiac vagal motoneurones (CVM). This is a preliminary investigation of the possible effects of BSP in altering the bradycardia of patients submitted to CA for diagnostic purpose. Patients were divided into two age-and racematched groups: control (C:N=45, age 58.6 + 1.6 years, mean arterial blood pressure (MAP) 109 + 2.4 mmHg, heart rate (HR) 79 + 2.9 bpm) and BSP-treated (B:N=14, age 58.9 + 2.1 years, MAP 111 + 4.5 mmHg, HR 76 + 3.4 bpm). The prevalent underlying pathology was coronary artery disease. Patients with acute angina, congestive heart failure, symptomatic arrhythmia and patients requiring atropine were excluded. CA was performed by a standard procedure using diatrizoate (MD-76() as contrast agent. The left and then the right coronary ostia were selectively catheterized and 8 ml of contrast medium was injected (over a period of 3 sec). HR was measured from ECG tracing before and after contrast injection into the left (LC) and right (RC) coronary arteries. Peak bradycardia was measured as the longest R-R interval during the first 15 sec after the injection minus the pre-injection R-R value, and reported as deltaR-R. Group B patients received BSP tablets 48 and 24 h before the examination (30 mg/day po). There was no statistically significant difference (P>0.05) in bradycardia between groups (C:LC=-147 + 23,RC=-155+25; B:LC=-143 + 44,RC=-234 + 56 msec). These results suggest that, in contrast to experimental animals, the central 5-HT1A receptors of humans are not relevant for modulating the excitability of CVM in the BJ reflex. However, since drugs and diseases can affect the responses, further studies are necessary to clarify this issue.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Bradicardia/induzido quimicamente , Buspirona/efeitos adversos , Angiografia Coronária , Receptores de Serotonina , Reflexo , Buspirona/administração & dosagem , Diatrizoato , Diatrizoato/administração & dosagem , Frequência Cardíaca , Hipertrofia Ventricular Esquerda , Injeções Intra-Arteriais , Estudos RetrospectivosRESUMO
Considerable experimental evidence suggests that central dopaminergic (DA) transmission is under serotonergic (5-HTergic) modulation. For instance, neuroleptic-induced catalepsy (NIC) in rodents, a behavior mainly due to blockade of DA receptors in the striatum, can be affected by 5-HTergic manipulation. It has been shown that ligands of 5-HT1A receptors (e.g. buspirone, gepirone) reduce NIC, while 5-HT2 receptor antagonists (e.g. ritanserin) do not affect this phenomenon. However, the role of 5-HT2 receptors in the modulation of NIC is still controversial and there is evidence from behavioral models other than NIC suggesting the existence of functional interaction between the two subtypes of 5-HT receptors. The present study was designed to evaluate the effect of ICI 170,809 (a selective 5-HT2 receptor antagonist) on NIC and to test the possible effect of this drug on the anticataleptic effect of gepirone (GP). Male Wistar rats weighing 300-350 g were used, and each animal (7 per group, 4 groups) was used only once. Catalepsy was induced with haloperiodol (H; 1 mg/kg, ip) and measured at 30-min intervals by means of a bar test. Animals received either ICI 170,809 (3 mg/kg, ip) or 0.9 percent saline(SL; 0.8 ml, ip) 30 min before H. At 110 min after H, the rats received GP (1 mg/kg, ip) or SL (0.8 ml, ip). GP significantly attenuated NIC (e.g. 739 + or - 106 s vs 1009 + or - 85 s for controls, at 150 min after H), while ICI 170,809 did not significantly affect the phenomenon (e.g. 978 + or - 89 s vs 1009 + or - s for controls, at 150 min after H). Pretreatment with ICI 170,809 did not significantly modify the anticataleptic effect of GP (e.g. 617 + or - 90 s vs 739 + or - 106 s for SL-pretreated animals, at 150 min after H). These results confirm reports of the anticataleptic effect of GP and the lack of effect of 5-HT2 receptor antagonists on NIC. Moreover, these data also suggest the absence of functional interactions between central 5-HT1A and 5-HT2 receptors in this model of DA transmission
Assuntos
Animais , Masculino , Ratos , Catalepsia/induzido quimicamente , Quinolinas/farmacologia , Receptores de Serotonina/fisiologia , Pirimidinas/antagonistas & inibidores , Ratos WistarRESUMO
Typical neuroleptics (e.g. haloperidol) can induce catalepsy in rodents. Selective 5-hydroxytryptamine1A (5-HT1A) receptor antagonists reduce neuroleptic-induced catalepsy (NIC), suggesting that this subtype of serotonin receptor plays a role in the modulation of nigrostriatal dopaminergic transmission. The present study was designed to evaluate the participation of other 5-HT receptor subtypes in NIC. Adult albino mice (both sexes, 26-35 g) were used. Catalepsy was induced with haloperidol (H; 1.5 mg/kg, ip) and measured at 30-min intervals by means of a bar test. Cyanopindolol (a 5-HT1B receptor antagonist), ICI 169,369 (a 5-HT1C/2 receptor antagonist) and granisetron (a 5-HT3 receptor antagonist) were used. Buspirone, a 5-HT1A partial antagonist, cisapride, a 5-HT3/5-HT4 ligand and clomipramine, a 5-HT neuronal uptake blocker, were also employed. These drugs were injected ip, 20 min before H, with each animal (9-10 per group) used only once. Cyanopindolol (0.3 mg/kg) or ICI 169,369 (5 mg/kg) did not significantly affect NIC (375 +/- 39 and 378 +/- 34 s vs 372 +/- 44 s for controls, at 2 h after H). Buspirone (1 mg/kg) reduced, while pretreatments with either granisetron (0.5 mg/kg), cisapride (5 mg/kg) or clomipramine (5 mg/kg) potentiated the cataleptic effect of H (107 +/- 19, 576 +/- 52, 815 +/- 76 and 800 +/- 97 s vs 374 +/- 40 s in the control group, at 2 h after H).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Animais , Masculino , Feminino , Camundongos , Buspirona/farmacologia , Catalepsia/tratamento farmacológico , Granisetron/farmacologia , Pindolol/análogos & derivados , Piperidinas/farmacologia , Quinolinas/farmacologia , Receptores de Serotonina , Catalepsia/induzido quimicamente , Haloperidol , Pindolol/farmacologia , Fatores de TempoRESUMO
Catalepsy induced by neuroleptics in rats can be modified by 5-hydroxytryptaminergic (5-HTergic) manipulation. For example, buspirone (BUS) and other central 5-HT1A receptor ligands reduce neuroleptic-induced catalepsy (NIC). The dorsal (DRN) and median (MRN) raphe nuclei are reported to be important sources of 5-HTergic projections to the basal ganglia, the site of action of neuroleptics in producing NIC. A previous study showed that lesion of DRN did not affect NIC or the anticataleptic effect of BUS. The present study was designed to evaluate the participation of MRN in NIC and in the anti-NIC effect of BUS. Twenty-four male Wistar rats (N = 6/group) weighing 220-250 g were used. Electrolytic lesion of MRN was carried out in anesthetized rats along with sham operations (electrode inserted but no current applied). Ten days later, the rats were injected with BUS (5 mg/kg, ip) or saline (1 ml, ip). Catalepsy was induced 20 min later with haloperidol (H; 1 mg/kg, ip) and measured at 30-min intervals by means of a bar test. The Costall per cent Naylor method of scoring (range 0-5 points) was used. Saline-injected MRN-lesioned rats displayed significantly lower catalepsy scores than sham-lesioned rats (1.5 +/- 0.2 vs 3.8 +/- 0.3 at 90 min after H). In sham-lesioned rats, BUS significantly reduced the catalepsy scores in comparison with saline-treated animals (1.3 +/- 0.2 vs 3.8 +/- 0.3 at 90 min after H). However, BUS was not able to further reduce NIC in the MRN-lesioned animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Animais , Masculino , Ratos , Antipsicóticos/farmacologia , Buspirona/farmacologia , Catalepsia/etiologia , Núcleos da Rafe/fisiologia , Antipsicóticos/antagonistas & inibidores , Catalepsia/tratamento farmacológico , Serotonina/farmacologiaRESUMO
The anxiolytic drug buspirone (BUS) and other central 5-HT-1A receptor ligands are capable of reducing neuroleptic-induced catalepsy in rodents. The dorsal raphe nucleus (DRN) is reported to be an important source of serotonergic projections to the basal ganglia, the site of neuroleptic action. The present study was designed to evaluate the participation of the DRN in the anticataleptic effect of BUS on male Wistar rats. Rats were submitted to electrolytic or sham DRN lesion under barbiturate anesthesia. Ten days later, the animals were injected with BUS (5 mg/kg,ip) or saline ( 1 ml, ip) and catalepsy was induced 20 min later with haloperidol (1 mg/kg, ip). Saline-injected DRN-lesioned and sham-lesioned rats displayed similar catalepsy score and BUS significantly and similarly reduced the catalepsy scores in both groups. The results suggest that, in producing anticataleptic effects, BUS interacts at sites other than the DRN. The participation of other raphe nuclei in the anticataleptic effect of BUS is currently under investigation
Assuntos
Animais , Ratos , Masculino , Buspirona/farmacologia , Catalepsia/tratamento farmacológico , Núcleos da Rafe/efeitos dos fármacos , Análise de Variância , Catalepsia/induzido quimicamente , Haloperidol , Ratos Wistar , Receptores de Serotonina/efeitos dos fármacosRESUMO
Neuroleptcs such as chlorpromazine and haloperidol are capable of inducing catalepsy in rodents. Non-selective 5-hydroxytryptamine (5-HT) antagonists such as methysergide reduce the cataleptic effect of haloperidol. The present study was designed to evaluate the particpation of 5-HT-1A receptors in chlorpromazine-induced catalepsy in mice. Pundolol and buspirone, two putative 5-HT-1A receptor ligands, were used. Pretreatment with these drugs reduced the cataleptic effect of chlorpromazine. Clomipramine, a 5-HT neuronal uptake blocker, reversed the inhibitory effect of buspirone. Pretreatment with clomipramine alone caused a potentiation of neuroleptic-induced catalepsy. These results suggest that central 5-HT-1A receptors play an important role in neuroleptic-induced catalepsy in mice
Assuntos
Camundongos , Animais , Masculino , Feminino , Buspirona/farmacologia , Catalepsia/induzido quimicamente , Clorpromazina/antagonistas & inibidores , Clomipramina/farmacologia , Haloperidol/antagonistas & inibidores , Pindolol/farmacologiaRESUMO
The medullary raphe are involved in the control of sympathetic activity during desynchonized sleep and in the modulation of nocicepotive sensory inpts. To determine the particpation cholinergic and opiate mechanisms in the control of sympathetic activity, we microinjected eserine, morphine and naloxone into the nucleus raphe obscurus (NRO) of urethane-anesthetized rats. Arterial blood pressure (BP) and renal nerve activity (RN) were recorded. Eserine and morphine induced significant reductions of RN and BP, while naloxone had no effect. It is suggested that cholinergic and opiate mechanisms particpate in the control of sympathetic activity by th NRO