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
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 , Animais , 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 , Masculino , Paroxetina/farmacologia , Ratos Wistar , Taxa Respiratória/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Sertralina/farmacologia , Sinais Vitais/efeitos dos fármacosRESUMO
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
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% (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%), 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%, -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
Formaldeído/antagonistas & inibidores , Nociceptividade/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Sertralina/farmacologia , Animais , Pressão Arterial/efeitos dos fármacos , Formaldeído/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Neurônios Aferentes/efeitos dos fármacos , Medição da Dor/efeitos dos fármacos , Ratos , 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
Activation of 5-hydroxytryptamine (5-HT) 5-HT(1A), 5-HT(2C), 5-HT(3), and 5-HT(7) receptors modulates the excitability of cardiac vagal motoneurones, but the precise role of 5-HT(2A/2B) receptors in these phenomena is unclear. We report here the effects of intracisternal (ic) administration of selective 5-HT(2A/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-HT(2A) antagonist; 0.1 µmol/kg), SB-204741 (a 5-HT(2B) 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-HT(2A) 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-HT(2B) receptor antagonists nor the vehicle changed the reflex. These data suggest that central 5-HT(2A) receptors modulate the central pathways of the parasympathetic component of the von Bezold-Jarisch reflex.
Assuntos
Bradicardia/fisiopatologia , Receptor 5-HT2A de Serotonina/fisiologia , Reflexo/efeitos dos fármacos , Nervo Vago/efeitos dos fármacos , Analgésicos/farmacologia , Animais , Atenolol/farmacologia , Biguanidas/farmacologia , Bradicardia/induzido quimicamente , Masculino , Ratos , 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 (cm(2))-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 mm(2)). 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/mm(2). 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
Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Terapia com Luz de Baixa Intensidade , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Cicatrização/efeitos da radiação , Animais , Celecoxib , Hélio/uso terapêutico , Masculino , Camundongos , Neônio/uso terapêutico , Cicatrização/efeitos dos fármacosRESUMO
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% 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%) or pre-hypertensive levels (6.6%) also had comorbidity for overweight and blood lipid abnormalities (14% for triglycerides, 44.7% for TC, 25.9% for LDL-C, 52% 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
Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Frequência Cardíaca/fisiologia , Lipídeos/sangue , Adolescente , Índice de Massa Corporal , Brasil/epidemiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Criança , Estudos Transversais , Teste de Esforço , Feminino , Glucose/análise , Humanos , Masculino , Prevalência , Fatores de Risco , EspirometriaRESUMO
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.