RESUMO
GABA(A) and GABA(B) receptors are present in the lateral parabrachial nucleus (LPBN), a pontine area involved with inhibitory mechanisms related to the control of sodium appetite. Activation of GABA(A) receptors in the LPBN induces strong ingestion of 0.3 M sodium chloride (NaCl) in normonatremic and euhydrated rats. In the present study, we investigated the effects of the GABA(B) receptor agonist baclofen, injected alone or combined with GABA(A) or GABA(B) receptor antagonists into the LPBN on 0.3 M NaCl, water, 0.06 M sucrose and food intake in normonatremic and euhydrated rats. Male Holtzman rats with stainless steel cannulas implanted bilaterally in the LPBN were used. In normonatremic and euhydrated rats, bilateral injections of baclofen (0.5 nmol/0.2 µl) into the LPBN induced 0.3 M NaCl (24.0±3.1 vs. saline: 2.0±0.8 ml/240 min) and water intake (10.6±1.4 vs. saline: 3.5±0.7 ml/240 min) in a two-bottle test. Injections of GABA(B) receptor antagonists CGP 35348 (50 nmol/0.2 µl) or 2-hydroxysaclofen (5 nmol/0.2 µl) or GABA(A) receptor antagonist bicuculline (1.6 nmol/0.2 µl) into the LPBN reduced 0.3 M NaCl (14.1±4.7 ml/240 min; 9.97±2.5 ml/210 min; 8.8±5.9 ml/240 min, respectively) and water intake induced by baclofen injected into the LPBN. Baclofen (0.5 nmol/0.2 µl) injected into the LPBN also induced 0.06 M sucrose intake (21.8±5.9 vs. saline: 5.0±2.6 ml/180 min). Urinary volume and sodium excretion had a tendency to decrease after baclofen injection into the LPBN, whereas arterial pressure and food intake were not affected. The results show that baclofen injected into the LPBN, in normonatremic and euhydrated rats, produces a natriorexigenic effect dependent on GABA(A) and GABA(B) receptor activation. The natriorexigenic effect is not secondary to alterations in blood pressure or sodium urinary excretion. In addition, baclofen injected into the LPBN also induces 0.06 M sucrose intake.
Assuntos
Baclofeno/farmacologia , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Agonistas dos Receptores de GABA-B/farmacologia , Ponte/efeitos dos fármacos , Solução Salina Hipertônica/metabolismo , Sacarose/metabolismo , Análise de Variância , Animais , Pressão Sanguínea/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Esquema de Medicação , Interações Medicamentosas , Antagonistas GABAérgicos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Natriurese/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Micção/efeitos dos fármacosRESUMO
Inhibitory serotonergic and cholecystokinergic mechanisms in the lateral parabrachial nucleus and central GABAergic mechanisms are involved in the regulation of water and NaCl intake. In the present study we investigated if the GABA(A) receptors in the lateral parabrachial nucleus are involved in the control of water, NaCl and food intake in rats. Male Holtzman rats with stainless steel cannulas implanted bilaterally into the lateral parabrachial nucleus were used. Bilateral injections of muscimol (0.2 nmol/0.2 microl) into the lateral parabrachial nucleus strongly increased 0.3 M NaCl (20.3+/-7.2 vs. saline: 2.6+/-0.9 ml/180 min) without changing water intake induced by the treatment with the diuretic furosemide combined with low dose of the angiotensin converting enzyme inhibitor captopril s.c. In euhydrated and satiated rats, bilateral lateral parabrachial nucleus injections of muscimol (0.2 and 0.5 nmol/0.2 microl) induced 0.3 M NaCl intake (12.1+/-6.5 and 32.5+/-7.3 ml/180 min, respectively, vs. saline: 0.4+/-0.2 ml/180 min) and water intake (5.2+/-2.0 and 7.6+/-2.8 ml/180 min, respectively, vs. saline: 0.8+/-0.4 ml/180 min), but no food intake (2+/-0.4 g/240 min vs. saline: 1+/-0.3 g/240 min). Bilateral lateral parabrachial nucleus injections of the GABA(A) antagonist bicuculline (1.6 nmol/0.2 microl) abolished the effects of muscimol (0.5 nmol/0.2 microl) on 0.3 M NaCl and water intake. Muscimol (0.5 nmol/0.2 microl) into the lateral parabrachial nucleus also induced a slight ingestion of water (4.2+/-1.6 ml/240 min vs. saline: 1.1+/-0.3 ml/240 min) when only water was available, a long lasting (for at least 2 h) increase on mean arterial pressure (14+/-4 mm Hg, vs. saline: -1+/-1 mm Hg) and only a tendency to increase urinary volume and Na+ and K+ renal excretion. Therefore the activation of GABA(A) receptors in the lateral parabrachial nucleus induces strong NaCl intake, a small ingestion of water and pressor responses, without changes on food intake.
Assuntos
Ingestão de Líquidos/fisiologia , Ingestão de Alimentos/fisiologia , Ponte/fisiologia , Receptores de GABA-A/fisiologia , Solução Salina Hipertônica/metabolismo , Análise de Variância , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Comportamento Animal , Bicuculina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Captopril/farmacologia , Diurese/efeitos dos fármacos , Diuréticos/farmacologia , Ingestão de Líquidos/efeitos dos fármacos , Interações Medicamentosas , Ingestão de Alimentos/efeitos dos fármacos , Furosemida/farmacologia , Agonistas GABAérgicos/farmacologia , Antagonistas GABAérgicos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Muscimol/farmacologia , Ponte/efeitos dos fármacos , Potássio/urina , Ratos , Ratos Sprague-Dawley , Sódio/urina , Fatores de TempoRESUMO
We investigated the effects of bilateral injections of the GABA receptor agonists muscimol (GABA A) and baclofen (GABA B) into the nucleus tractus solitarius (NTS) on the bradycardia and hypotension induced by iv serotonin injections (5-HT, 2 microg/rat) in awake male Holtzman rats. 5-HT was injected in rats with stainless steel cannulas implanted bilaterally in the NTS, before and 5, 15, and 60 min after bilateral injections of muscimol or baclofen into the NTS. The responses to 5-HT were tested before and after the injection of atropine methyl bromide. Muscimol (50 pmol/50 nl, N = 8) into the NTS increased basal mean arterial pressure (MAP) from 115 +/- 4 to 144 +/- 6 mmHg, did not change basal heart rate (HR) and reduced the bradycardia (-40 +/- 14 and -73 +/- 26 bpm at 5 and 15 min, respectively, vs -180 +/- 20 bpm for the control) and hypotension (-11 +/- 4 and -14 +/- 4 mmHg, vs -40 +/- 9 mmHg for the control) elicited by 5-HT. Baclofen (12.5 pmol/50 nl, N = 7) into the NTS also increased basal MAP, but did not change basal HR, bradycardia or hypotension in response to 5-HT injections. Atropine methyl bromide (1 mg/kg body weight) injected iv reduced the bradycardic and hypotensive responses to 5-HT injections. The stimulation of GABA A receptors in the NTS of awake rats elicits a significant increase in basal MAP and decreases the cardiac Bezold-Jarisch reflex responses to iv 5-HT injections.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Agonistas GABAérgicos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Serotonina/farmacologia , Núcleo Solitário/efeitos dos fármacos , Animais , Baclofeno/farmacologia , Bradicardia/fisiopatologia , Hipotensão/fisiopatologia , Masculino , Muscimol/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de GABA-A/fisiologia , Serotonina/administração & dosagem , Núcleo Solitário/fisiologiaRESUMO
We investigated the effects of bilateral injections of the GABA receptor agonists muscimol (GABA A) and baclofen (GABA B) into the nucleus tractus solitarius (NTS) on the bradycardia and hypotension induced by iv serotonin injections (5-HT, 2 æg/rat) in awake male Holtzman rats. 5-HT was injected in rats with stainless steel cannulas implanted bilaterally in the NTS, before and 5, 15, and 60 min after bilateral injections of muscimol or baclofen into the NTS. The responses to 5-HT were tested before and after the injection of atropine methyl bromide. Muscimol (50 pmol/50 nl, N = 8) into the NTS increased basal mean arterial pressure (MAP) from 115 ± 4 to 144 ± 6 mmHg, did not change basal heart rate (HR) and reduced the bradycardia (-40 ± 14 and -73 ± 26 bpm at 5 and 15 min, respectively, vs -180 ± 20 bpm for the control) and hypotension (-11 ± 4 and -14 ± 4 mmHg, vs -40 ± 9 mmHg for the control) elicited by 5-HT. Baclofen (12.5 pmol/50 nl, N = 7) into the NTS also increased basal MAP, but did not change basal HR, bradycardia or hypotension in response to 5-HT injections. Atropine methyl bromide (1 mg/kg body weight) injected iv reduced the bradycardic and hypotensive responses to 5-HT injections. The stimulation of GABA A receptors in the NTS of awake rats elicits a significant increase in basal MAP and decreases the cardiac Bezold-Jarisch reflex responses to iv 5-HT injections.
Assuntos
Animais , Masculino , Ratos , Pressão Sanguínea/efeitos dos fármacos , Agonistas GABAérgicos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Serotonina/farmacologia , Núcleo Solitário/efeitos dos fármacos , Baclofeno/farmacologia , Bradicardia/fisiopatologia , Hipotensão/fisiopatologia , Muscimol/farmacologia , Ratos Sprague-Dawley , Receptores de GABA-A/fisiologia , Serotonina/administração & dosagem , Núcleo Solitário/fisiologiaRESUMO
In the present study we investigated the effects of bilateral microinjection into the lateral commissural nucleus tractus solitarius (NTS) of 2-methyl-5-HT, a 5-HT3 receptor agonist, on the bradycardic response of the von Bezold-Jarisch reflex of awake rats. We evaluated mainly the bradycardic response because in previous studies we documented that the hypotensive response of the von-Bezold-Jarisch reflex in awake rats is secondary to the intense bradycardic response. The Bezold-Jarisch reflex was activated by intravenous injection of serotonin (8 microg/kg) in awake rats before and 1, 3, 10, 20 and 60 min after bilateral microinjection of 2-methyl-5-HT (5 nmol/50 nl, n = 8) into the NTS. Microinjections of 2-methyl-5-HT into the NTS produced a significant increase in basal mean arterial pressure [(MAP), 97 +/- 4 vs. 114 +/- 4 mmHg), no changes in basal heart rate and a significant reduction in bradycardic (-78 +/- 19; -94 +/- 24 and -107 +/- 21 bpm) and hypotensive (-16 +/- 4; -10 +/- 5 and -17 +/- 4 mmHg) responses to activation of the von Bezold-Jarisch reflex at 3, 10 and 20 min, respectively, when compared with the control value (-231 +/- 13 bpm and -43 +/- 4 mmHg). The data of the present study suggest that serotonin acting on 5-HT3 receptors in the NTS may play an important inhibitory neuromodulatory role in the bradycardic response to activation of the von Bezold-Jarisch reflex.
Assuntos
Bradicardia/fisiopatologia , Receptores de Serotonina/fisiologia , Reflexo Anormal/efeitos dos fármacos , Agonistas do Receptor de Serotonina/farmacologia , Serotonina/farmacologia , Núcleo Solitário/efeitos dos fármacos , Análise de Variância , Animais , Nível de Alerta , Pressão Sanguínea/efeitos dos fármacos , Bradicardia/induzido quimicamente , Frequência Cardíaca/efeitos dos fármacos , Masculino , Microinjeções , Fibras Nervosas/efeitos dos fármacos , Fibras Nervosas/fisiologia , Inibição Neural/efeitos dos fármacos , Sistema Nervoso Parassimpático/citologia , Sistema Nervoso Parassimpático/efeitos dos fármacos , Sistema Nervoso Parassimpático/fisiologia , Ratos , Ratos Wistar , Receptores 5-HT3 de Serotonina , Serotonina/análogos & derivados , Núcleo Solitário/citologia , Núcleo Solitário/fisiologia , Sistema Nervoso Simpático/citologia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Transmissão Sináptica/efeitos dos fármacosRESUMO
In the present study we evaluated the effects of bilateral microinjection of muscimol (a GABA(A) receptor agonist) and baclofen (a GABA(B) receptor agonist) into the lateral commissural nucleus tractus solitarii (NTS) of awake rats on the gain of the baroreflex (BG) activated by a short duration (10-15 s) infusion of phenylephrine (Phe, 2.5 microg/0.05 ml, i.v.). Microinjection of muscimol (50 pmol/50 nl, n=8) into the NTS produced a significant increase in baseline mean arterial pressure ((MAP) 122+/-6 vs. 101+/-2 mmHg), no changes in baseline heart rate (HR) and a reduction in BG (-1.59+/-0. 1 vs. -0.69+/-0.1 beats/mmHg). Microinjection of baclofen (6.25 pmol/50 nl, n=6) into the NTS also produced a significant increase in baseline MAP (138+/-5 vs. 103+/-2 mmHg), no changes in baseline HR and a reduction in BG (-1.54+/-0.3 vs. -0.53+/-0.2 beats/mmHg). Considering that the reduction in BG could be secondary to the increase in MAP in response to microinjection of muscimol (n=6) or baclofen (n=7) into the NTS, in these two groups of rats we brought the MAP back to baseline by infusion of sodium nitroprusside (NP, 3.0 microg/0.05 ml, i.v.). Under these conditions, we verified that the BG remained significantly reduced after muscimol (-1.49+/-0.2 vs. -0.35+/-0.2 beats/mmHg) and after baclofen (-1.72+/-0.2 vs. -0.33+/-0.2 beats/mmHg) when compared to control. Reflex tachycardia was observed during the normalization of MAP by NP infusion and, in order to prevent the autonomic imbalance from affecting BG, we used another group of rats treated with atenolol (5 mg/kg, i.v.), a beta1 receptor antagonist. In rats previously treated with atenolol and submitted to NP infusion, we verified that BG remained reduced after microinjection of muscimol or baclofen into the NTS. The data show that activation of GABA(A) and GABA(B) receptors, independently of the changes in the baseline MAP or HR, inhibited the neurons of the NTS involved in the parasympathetic component of the baroreflex.
Assuntos
Barorreflexo/fisiologia , Pressão Sanguínea/fisiologia , Bradicardia , Frequência Cardíaca/fisiologia , Receptores de GABA-A/fisiologia , Receptores de GABA-B/fisiologia , Núcleo Solitário/fisiologia , Animais , Anti-Hipertensivos/farmacologia , Baclofeno/farmacologia , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Bradicardia/induzido quimicamente , Cardiotônicos , Agonistas GABAérgicos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Muscimol/farmacologia , Nitroprussiato/farmacologia , Fenilefrina , Ratos , Ratos Wistar , Receptores de GABA-A/efeitos dos fármacos , Receptores de GABA-B/efeitos dos fármacos , Núcleo Solitário/efeitos dos fármacosRESUMO
Previous reports have described that glutamate ionotropic receptors in the nucleus tractus solitarius (NTS) are involved in the reflex control of heart rate, and that such a control can be inhibited by NTS-5-HT(3) receptor stimulation. In the present study, we examined in urethane anaesthetized rats the effects of intra-NTS microinjection of 1-(m-chlorophenyl)-biguanide (CPBG), a potent and selective 5-HT(3) receptor agonist, on the cardiovascular responses to local administration of glutamate ionotropic receptor agonists. Intra-NTS microinjection of CPBG reduced the atropine-sensitive bradycardia elicited by local microinjection of NMDA without affecting the cardiovascular responses to intra-NTS microinjections of AMPA or kainic acid. The reduction by CPBG of the NMDA-evoked cardiac response was blocked by prior intra-NTS microinjection of granisetron, a 5-HT(3) receptor antagonist, as well as bicuculline, a GABA(A) receptor antagonist. These results suggest that the stimulation of NTS 5-HT(3) receptors specifically reduces, via a GABA-dependent mechanism, the cardiac response to local NMDA administration.
Assuntos
Agonistas de Aminoácidos Excitatórios/farmacologia , Frequência Cardíaca/efeitos dos fármacos , N-Metilaspartato/farmacologia , Receptores de Serotonina/efeitos dos fármacos , Núcleo Solitário/fisiologia , Animais , Barorreflexo/efeitos dos fármacos , Bicuculina/farmacologia , Biguanidas/farmacologia , Agonistas de Aminoácidos Excitatórios/administração & dosagem , Antagonistas GABAérgicos/farmacologia , Granisetron/farmacologia , Hemodinâmica/efeitos dos fármacos , Masculino , Microinjeções , N-Metilaspartato/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptores de Ácido Caínico/antagonistas & inibidores , Receptores 5-HT3 de Serotonina , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Sistema Nervoso Simpático/efeitos dos fármacos , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/farmacologiaRESUMO
In the present study we analyzed effects of bilateral microinjections of muscimol (a GABAA agonist) and baclofen (a GABAB agonist) into the nucleus tractus solitarius (NTS) on bradycardic and pressor responses to chemoreflex activation (potassium cyanide, 40 micrograms/rat iv) in awake rats. Bilateral microinjections of muscimol (25 and 50 pmol/50 nl) into the NTS increased baseline mean arterial pressure (MAP): 119 +/- 8 vs. 107 +/- 2 mmHg (n = 6) and 121 +/- 8 vs. 103 +/- 3 mmHg (n = 6), respectively. Muscimol at 25 pmol/50 nl reduced the bradycardic response to chemoreflex activation 5 min after microinjection; with 50 pmol/50 nl the bradycardic response to chemoreflex activation was reduced 5, 15, 30, and 60 min after microinjection. Neither muscimol dose produced an effect on the pressor response of the chemoreflex. Effects of muscimol (50 pmol/50 nl) on basal MAP and on the bradycardic response of the chemoreflex were prevented by prior microinjection of bicuculline (a GABAA antagonist, 40 pmol/50 nl) into the NTS. Bilateral microinjections of baclofen (12.5 and 25 pmol/50 nl) into the NTS produced an increase in baseline MAP [137 +/- 9 vs. 108 +/- 4 (n = 7) and 145 +/- 5 vs. 105 +/- 2 mmHg (n = 7), respectively], no changes in basal heart rate, and no effects on the bradycardic response; 25 pmol/50 nl only attenuated the pressor response to chemoreflex activation. The data show that activation of GABAA receptors in the NTS produces a significant reduction in the bradycardic response, whereas activation of GABAB receptors produces a significant reduction in the pressor response of the chemoreflex. We conclude that 1) GABAA but not GABAB plays an inhibitory role in neurons of the lateral commissural NTS involved in the parasympathetic component of the chemoreflex and 2) attenuation of the pressor response of the chemoreflex by activation of GABAB receptors may be due to inhibition of sympathoexcitatory neurons in the NTS or may be secondary to the large increase in baseline MAP produced by baclofen.
Assuntos
Bradicardia/prevenção & controle , Células Quimiorreceptoras/fisiologia , Receptores de GABA-A/metabolismo , Reflexo/fisiologia , Núcleo Solitário/metabolismo , Animais , Baclofeno/farmacologia , Bradicardia/etiologia , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Agonistas GABAérgicos/farmacologia , Masculino , Microinjeções , Muscimol/efeitos adversos , Muscimol/farmacologia , Ratos , Ratos Wistar , Receptores de GABA-B/metabolismo , Reflexo/efeitos dos fármacos , Núcleo Solitário/efeitos dos fármacosRESUMO
In the present study, we analyzed in conscious rats the effects of microinjections of serotonin (5-HT; pmol range) into the nucleus of the solitary tract (NTS) on basal mean arterial pressure (MAP) and heart rate (HR) and also on the reflex bradycardia induced by the activation of the baro- and chemoreflex evaluated 1 min after 5-HT microinjection into the NTS. The data show that unilateral microinjection of 5-HT in the picomolar range into the NTS of unanesthetized rats produced a dose-dependent decrease in MAP and HR, which was blocked by previous microinjection of ketanserin (250 pmol/50 nl) into the NTS. The changes in MAP and HR induced by 5-HT were of very short duration, with a return to baseline values a few seconds later. The cardiovascular responses to baro- or chemoreflex activation 1 min after 5-HT microinjection into the NTS did not differ from the control, indicating that low doses of 5-HT produced no effect on the cardiovascular reflexes tested at that time. The present data show that, as also observed in anesthetized rats, the microinjection of picomolar doses of 5-HT into the NTS elicits the typical cardiovascular responses to baroreceptor activation. These effects, hypotension and bradycardia, seem to be mediated by 5-HT2 receptors because both were blocked by a selective 5-HT2 receptor antagonist. However, since microinjection of 5-HT (1 pmol) into the NTS produced no changes in the cardiovascular responses to the baro- and chemoreflex activated 1 min later, the role of 5-HT2 receptors in the processing of the cardiovascular afferent messages in the NTS remains to be elucidated.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Células Quimiorreceptoras/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Pressorreceptores/fisiologia , Serotonina/farmacologia , Núcleo Solitário/fisiologia , Animais , Barorreflexo/efeitos dos fármacos , Mapeamento Encefálico , Células Quimiorreceptoras/efeitos dos fármacos , Lateralidade Funcional , Masculino , Microinjeções , Cianeto de Potássio/farmacologia , Pressorreceptores/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores de Serotonina/efeitos dos fármacos , Receptores de Serotonina/fisiologia , Reflexo/efeitos dos fármacos , Serotonina/administração & dosagem , Núcleo Solitário/efeitos dos fármacosRESUMO
In the present study we investigated the effects of microinjection into the commissural nucleus tractus solitarius (NTS) of unanesthetized rats of 2-methylserotonin (2-methyl-5-HT), a 5-HT3 receptor agonist, on the cardiac component of the baro- and chemoreflexes. The study was performed in conscious freely moving rats in order to avoid the possible effects of anesthetics on the cardiovascular responses to microinjection of neuroactive substances into the NTS. The baroreflex (phenylephrine, 0.5-2.0 micrograms/kg, i.v.) and the chemoreflex (potassium cyanide, 40 micrograms/rat, i.v) were activated in different groups of rats before and after bilateral microinjection of 2-methyl-5-HT into the NTS. Microinjections of 2-methyl-5-HT (5 nmol/50 nl) into the NTS produced a significant increase in basal mean arterial pressure (101 +/- 3 versus 125 +/- 8 mmHg), no changes in basal HR and a significant reduction in the reflex bradycardia triggered by baroreflex activation at 3 (-28 +/- 7 bpm), 10 (-35 +/- 4 bpm) and 20 min (-34 +/- 5 bpm) in comparison with the control value (-68 +/- 9 bpm). A similar reduction in the bradycardic response to chemoreflex activation was observed at 3 (-94 +/- 35 bpm), 10 (-98 +/- 38 bpm) and 20 min (-110 +/- 29 bpm) after 2-methyl-5-HT in comparison with the control value (-178 +/- 19 bpm). The effect of 2-methyl-5-HT on the basal mean arterial pressure and on the bradycardia evoked by stimulation of the baro- and chemoreflexes was blocked by pretreatment with granisetron bilaterally microinjected (500 pmol/50 nl) into the NTS. The data show that the stimulation of 5-HT3 receptors in the NTS of unanesthetized rats elicits a significant increase in basal mean arterial pressure and decreases the bradycardic response to baro- or chemoreflex activation.
Assuntos
Bradicardia/tratamento farmacológico , Células Quimiorreceptoras/fisiologia , Pressorreceptores/fisiologia , Agonistas do Receptor de Serotonina/farmacologia , Serotonina/análogos & derivados , Animais , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Microinjeções , Ratos , Ratos Wistar , Serotonina/farmacologiaRESUMO
We studied the effect of the alpha 1- and alpha 2-adrenergic receptors of the lateral hypothalamus (LH) on the control of water intake induced by injection of carbachol into the medial septal area (MSA) of adult male Holtzman rats (250-300 g) implanted with chronic stainless steel cannulae into the LH and MSA. The volume of injection was always 1 microliter and was injected over a period of 30-60 s. For control, 0.15 M NaCl was used. Clonidine (20 nmol) but not phenylephrine (160 nmol) injected into the LH inhibited water intake induced by injection of carbachol (2 nmol) into the MSA, from 5.4 +/- 1.2 ml/h to 0.3 +/- 0.1 and 3.0 +/- 0.9 ml/h, respectively (N = 26). When we injected yohimbine (80 nmol) + clonidine (20 nmol) and prazosin (40 nmol) + clonidine (20 nmol) into the LH, water intake induced by injection of carbachol into the MSA was inhibited from 5.4 +/- 1.2 ml/h to 0.8 +/- 0.5 and 0.3 +/- 0.2 ml/h, respectively (N = 19). Water intake induced by carbachol (2 nmol) injected into the MSA was decreased by previous injection of yohimbine (80 nmol) + phenylephrine (160 nmol) and prazosin (40 nmol) + phenylephrine (160 nmol) from 5.4 +/- 1.2 ml/h to 1.0 +/- 0.7 and 1.8 +/- 0.8 ml/h, respectively (N = 16). The cannula reached both the medial septal area in its medial portion and the lateral hypothalamus. It has been suggested that the different pathways for induction of drinking converge on a final common pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Carbacol/farmacologia , Ingestão de Líquidos/efeitos dos fármacos , Região Hipotalâmica Lateral/efeitos dos fármacos , Receptores Adrenérgicos alfa/fisiologia , Receptores Colinérgicos/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Clonidina/farmacologia , Masculino , Fenilefrina/farmacologia , Prazosina/farmacologia , Ratos , Ratos Sprague-Dawley , Ioimbina/farmacologiaRESUMO
We studied the effect of the Ó1-and Ó2-adrenergic receptors of the lateral hypothalamus (LH) on the control of water intake induced by injection of carbachol into the medial septal area (MSA) of adult male Holtzman rats (250-300g) implanted with chronic stainless steel cannulae into the LH and MSA. The volume of injection was always 1 µl and was injected over a period of 30-60 s. For control, 0.15MNaCl was used. Clonidine (20 nmol) but not phenylephrine (160 nmol) injected into the LH inhibited water intake induced by injection of carbachol (2 nmol) into the MSA, from 5.4 ñ 1.2ml/h to 0.3 ñ 0.1 and 3.0 ñ 0.9 ml/h, respectively (N=26). When we injected yohimbine (80nmol) + clonidine (20nmol) and prazosin (40nmol) + clonidine (20nmol) into the LH, water intake induced by injection of carbachol into the MSA was inhibited from 5.4 ñ 1.2 ml/h to 0.8 ñ 0.5 and 0.3 ñ 0.2 ml/h, respectively (N=19). Water intake induced by carbachol (2nmol) injected into the MSA was decreased by previous injection of yohimbine (80 nmol) + phenylephrine (160 nmol) and prazosin (40 nmol) + phenylephrine (160 nmol) from 5.4 ñ 1.2ml/h to 1.0 ñ 0.7 and 1.8 ml/h, respectively (N = 16). The cannula reached both the medial septal area in its medial portion and the lateral hypothalamus. It has been suggested that the different pathways for induction of drinking converge on a final common pathway. Thus, adrenergic stimulation of Ó2-adrenoceptors of LH can influence this final common pathway
Assuntos
Animais , Masculino , Ratos , Carbacol/farmacologia , Ingestão de Líquidos , Receptores Adrenérgicos alfa/fisiologia , Receptores Colinérgicos , Região Hipotalâmica Lateral , Clonidina/farmacologia , Fenilefrina/farmacologia , Prazosina/farmacologia , Ratos Sprague-Dawley , Ioimbina/farmacologiaRESUMO
In the present experiments, we investigated a possible involvement of noradrenergic receptors of the lateral hypothalamus (LH) in the water intake and pressor response induced by cholinergic stimulation of the medial septal area (MSA) in rats. The cholinergic agonist carbachol (2 nmol) injected into the MSA induced water intake and pressor response. The injection of an alpha 2-adrenergic agonist, clonidine (20 and 40 nmol), but not of an alpha 1-adrenergic agonist, phenylephrine (80 and 160 nmol), into the LH inhibits the water intake induced by carbachol injected into the MSA. The injection of clonidine or phenylephrine into the LH produced no change in the MAP increase induced by carbachol injected into the MSA. The present results suggest that adrenergic pathways involving the LH are important for the water intake, but not for the pressor response, induced by cholinergic activation of the MSA.
Assuntos
Pressão Sanguínea/fisiologia , Ingestão de Líquidos/fisiologia , Região Hipotalâmica Lateral/fisiologia , Parassimpatomiméticos/farmacologia , Septo Pelúcido/fisiologia , Sistema Nervoso Simpático/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Carbacol/farmacologia , Clonidina/farmacologia , Ingestão de Líquidos/efeitos dos fármacos , Masculino , Vias Neurais/fisiologia , Fenilefrina/farmacologia , Ratos , Ratos EndogâmicosRESUMO
In the present study, we investigated the effect of phenylephrine and clonidine (alpha 1- and alpha 2-adrenoceptor agonists, respectively) injected into the lateral preoptic area (LPOA) on the water intake induced by water deprivation in rats. In addition, the effects of prior injections of prazosin and yohimbine (alpha 1- and alpha 2-adrenoceptor antagonists, respectively) into the LPOA on the antidipsogenic action of phenylephrine and clonidine were investigated. After 30 h of water deprivation, the water intake of rats in a control experiment (saline injection) was 10.5 +/- 0.8 ml/h. Injection of clonidine (5, 10, 20, and 40 nmol) into the LPOA reduced water intake to 6.3 +/- 0.9, 4.9 +/- 0.8, 3.6 +/- 1.0, and 2.2 +/- 0.7 ml/h, respectively. Similar reductions occurred after injection of 80 and 160 nmol phenylephrine into the LPOA (6.2 +/- 1.6 and 4.8 +/- 1.3 ml/h, respectively). Pretreatment with prazosin (40 nmol) abolished the antidipsogenic action of an 80-nmol dose of phenylephrine (11.3 +/- 1.1 ml/h) and reduced the effect of a 20-nmol dose of clonidine (7.4 +/- 1.4 ml/h). Yohimbine (20, 40, and 80 nmol), previously injected, produced no significant changes in the effects of either phenylephrine or clonidine. The present results show that phenylephrine and clonidine injected into the LPOA induce an antidipsogenic effect in water-deprived rat. They also suggest an involvement of alpha 1-adrenoceptors in this effect. A possible participation of imidazole receptors in the effect of clonidine should also be taken into account.