RESUMO
The 5-hydroxytryptamine (5-HT)(1A) receptor system plays a prominent role in a variety of physiological functions and behavior and regulation of this responsiveness of the receptor system has been implicated in the central regulation of water intake and urinary excretion. The lateral septal area (LSA) exhibits a high density of 5-HT(1A) receptors, as well as a subpopulation of oxytocin (OT) receptors. Here we report the effects of pMPPF (a selective 5-HT(1A) antagonist), d(CH(2))(5)[Tyr(Me)(2)Thr(4), Orn(5), Tyr(NH(2))(9)]-vasotocin (an OT antagonist), and that 5-HT(1A) receptor system is regulated as a consequence of activation of the Na(+) channel by veratridine. Cannulae were implanted into the LSA of rats to enable the introduction of the drugs. Injections of 8-OH-DPAT (a 5-HT(1A) agonist) blocked water intake and increased urinary excretion, while pMPPF or the OT antagonist injected bilaterally before 8-OH-DPAT blocked its inhibitory effect on water intake and its diuretic effect. In contrast, increases in extracellular sodium levels induced by the sodium channel modulator, veratridine, enhanced 5-HT(1A) responsiveness for water intake and reduced the diuretic effects induced by 8-OH-DPAT. These trials demonstrated that the responsiveness of the 5-HT(1A) receptor system in the LSA can be enhanced or depressed as a consequence of an induced rise in extracellular sodium.
Assuntos
Ingestão de Líquidos/fisiologia , Receptor 5-HT1A de Serotonina/fisiologia , Núcleos Septais/fisiologia , Micção/fisiologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Análise de Variância , Animais , Cateteres de Demora , Ingestão de Líquidos/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Ocitocina/antagonistas & inibidores , Receptores de Ocitocina/fisiologia , Núcleos Septais/efeitos dos fármacos , Estatísticas não Paramétricas , Micção/efeitos dos fármacosRESUMO
Several reports have revealed a high density of 5-HT(1A) receptors in the lateral septal area (LSA), as well as a subpopulation of oxytocin (OT) receptors. Increasing evidence shows that 5-HT(1A) and OT neurons inhibit sodium urinary excretion. The aim of this study was to investigate the part played by serotonergic (5-HT(1A)) and oxytocinergic receptors in the LSA in the sodium intake induced in rats by sodium depletion followed by 24h deprivation. Cannulae were implanted bilaterally into the LSA of rats to enable the introduction of receptor ligands into that brain area. Serotonergic injections of 5-HT (10, 20, and 40 microg/0.2 microL) reduced 1.8% NaCl solution intake, but injections (1, 2, and 4 microg/0.2 microL) of 8-OH-DPAT, a 5-HT(1A) agonist, were more effective than 5-HT in reducing 1.8% NaCl intake. Pretreatment of the LSA with the 5-HT(1A) antagonist pMPPF partially reduced the inhibitory effect of 5-HT and totally reversed the effects of 8-OH-DPAT on 1.8% NaCl intake induced by sodium depletion. Previous treatment with the potent oxytocin receptor antagonist d(CH(2))(5)[Tyr(Me)(2)Thr(4), Orn(5), Tyr(NH(2))(9)]-vasotocin also totally blocked the inhibitory effects of 5-HT or 8-OH-DPAT on 1.8% NaCl intake. These results show that 5-HT(1A) serotonergic receptors in the LSA, including some that interact with the oxytocinergic system, modulate sodium intake induced by sodium loss in rats.
Assuntos
Receptor 5-HT1A de Serotonina/metabolismo , Receptores de Ocitocina/metabolismo , Núcleos Septais/metabolismo , Sódio na Dieta/metabolismo , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Injeções Intraventriculares , Masculino , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Serotonina/farmacologia , Serotoninérgicos/farmacologiaRESUMO
The paraventricular nucleus (PVN) may be considered as a dynamic mosaic of chemically-specified subgroups of neurons. 5-HT(1A) is one of the prime receptors identified and there is expressed throughout all magnocellular regions of the PVN. Several reports have demonstrated that a subpopulation of the magnocellular neurons expressing 5-HT(1A) receptors are oxytocin (OT) neurons and activation of 5-HT(1A) receptors in the PVN increases the plasma OT. Increasing evidence shows that OT inhibits water intake and increases urinary excretion in rats. The aim of this study was to investigate the role of serotonergic 5-HT(1A) receptors in the lateral-medial posterior magnocellular region of the PVN in the water intake and diuresis induced by 24 h of water deprivation. Cannulae were implanted in the PVN of rats. 5-HT injections in the PVN reduced water intake and increased urinary excretion. 8-OH-DPAT (a 5-HT(1A) agonist) injections blocked the water intake and increased urinary output in all the periods of the observation. pMPPF (a 5-HT(1A) antagonist) injected bilaterally before the 8-OH-DPAT blocked its inhibitory effect on water intake and its diuretic effect. We suggest that antidipsogenic and diuretic responses seem to be mediated via 5-HT(1A) receptors of the lateral-medial posterior magnocellular region of the PVN in water-deprived rats.
Assuntos
Diurese/fisiologia , Ingestão de Líquidos/fisiologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Receptor 5-HT1A de Serotonina/metabolismo , 8-Hidroxi-2-(di-n-propilamino)tetralina/administração & dosagem , 8-Hidroxi-2-(di-n-propilamino)tetralina/agonistas , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Aminopiridinas/administração & dosagem , Aminopiridinas/antagonistas & inibidores , Aminopiridinas/farmacologia , Animais , Diurese/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Interações Medicamentosas , Masculino , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Piperazinas/administração & dosagem , Piperazinas/antagonistas & inibidores , Piperazinas/farmacologia , Ratos , Ratos Sprague-Dawley , Serotonina/administração & dosagem , Serotonina/metabolismo , Serotonina/farmacologia , Antagonistas da Serotonina/administração & dosagem , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/administração & dosagem , Agonistas do Receptor de Serotonina/farmacologia , Fatores de Tempo , Privação de ÁguaRESUMO
We investigated the influence of voltage-dependent calcium channels and nitric oxide (NO) on angiotensin II (ANG II)-pressor effect injected into subfornical organ (SFO). The influence of NO on nifedipine antipressor action has also been studied by utilizing N(W)-nitro-L-arginine methyl ester (L-NAME) (20 mug x 0.2 mul(-1)) a nitric oxide synthase inhibitor (NOSI) and 7-nitroindazole (7-NIT) (20 mug x 0.2 mul(-1)), a specific neuronal nitric oxide synthase inhibitor (nNOSI). We have also investigated the role of losartan and PD123319, selective ANG II AT(1) and AT(2) receptor nonpeptide antagonists, in the pressor effect of ANG II and in the effect of L-NAME and 7-NIT, injected into the SFO. Adult male Holtzman rats (220 to 280 g) were anesthetized with ketamine (80 mg/kg(-1) of body weight) plus xylazine (7 mg/kg(-1) of body weight), placed in a stereotaxic apparatus (David Kopf model for rats), and implanted with cannula into the SFO. Direct mean arterial blood pressure (MAP) was recorded in conscious rats in a test cage, without access to food or water. The previously implanted catheter into femoral artery was connected to a Statham (P23 Db) pressure transducer (Statham-Gould, Valley View, OH) coupled to a multichannel recorder (PowerLab Multirecord). MAP increased after ANG II injection. Pre-treatment with nifidipine (50 mug x 0.2 mul(-1) or 100 mug x 0.2 mul(-1)) followed by 25 pmol x 0.2 mul(-1) of ANG II, decreased ANG II-pressor effect. L-NAME and 7-NIT increased the elevation in MAP induced by ANG II, which was blocked by the prior injection of nifedipine. The AT(1) angiotensin antagonist losartan injected into the SFO blocked the effect of ANG II and the effects of L-NAME and 7-NIT while PD123319 did not. These results provide evidence that ANG II-pressor effect is influenced by nitrergic pathways that utilize L-type calcium channels in the SFO.
RESUMO
In this study we investigated the influence of d(CH(2))(5)-Tyr (Me)-AVP (A(1)AVP) and [Adamanteanacatyl(1),D-ET-D-Tyr(2), Val(4), aminobutyril(6),A(8,9)]-AVP (A(2)AVP), antagonists of V(1) and V(2) arginine(8)-vasopressin (AVP) receptors, respectively, as well as the effects of losartan and CGP42112A, antagonists of angiotensin II (ANGII) AT(1) and AT(2,) receptors, respectively, on water and 0.3 M sodium intake induced by water deprivation or sodium depletion (furosemide treatment) and enhanced by AVP injected into the medial septal area (MSA). A stainless steel cannula was implanted into the medial septal area (MSA) of male Holtzman rats AVP injection enhanced water and sodium intake in a dose-dependent manner. Pretreatment with V(1) antagonist injected into the MSA produced a dose-dependent reduction, whereas prior injection of V(2) antagonist increased, in a dose-dependent manner, the water and sodium responses elicited by the administration of AVP. Both AT(1) and AT(2) antagonists administered into the MSA elicited a concentration-dependent decrease in water and sodium intake induced by AVP, while simultaneous injection of the two antagonists was more effective in decreasing AVP responses. These results also indicate that the increase in water and sodium intake induced by AVP was mediated primarily by MSA AT(1) receptors.
Assuntos
Apetite/fisiologia , Química Encefálica/fisiologia , Receptores de Angiotensina/metabolismo , Receptores de Vasopressinas/metabolismo , Septo do Cérebro/metabolismo , Cloreto de Sódio na Dieta/farmacologia , Sódio/deficiência , Sede/fisiologia , Vasopressinas/farmacologia , Privação de Água/fisiologia , Animais , Diuréticos/farmacologia , Ingestão de Líquidos/fisiologia , Eletrodos Implantados , Furosemida/farmacologia , Losartan/farmacologia , Oligopeptídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Septo do Cérebro/anatomia & histologiaRESUMO
We have studied the effects of L-NG-nitro arginine methyl esther (L-NAME), L-arginine (LAR), inhibitor and a donating nitric oxide agent on the alterations of salivary flow, water intake, arterial blood pressure (MAP) and heart rate (HR) induced by the injection pilocarpine into the subfornical organ (SFO). Rats (Holtzman 250-300 g) were anesthetized with 2, 2, 2-tribromoethanol (20 mg/100 kg b. wt.) and a stainless steel cannula were implanted into their SFO. The volume of injection was 0.2 microl. The amount of saliva secretion was studied over a 5-min period. Pilocarpine (40 microg), L-NAME (40 microg) and LAR (30 microg) were used in all experiments for the injection into the SFO. Pilocarpine (10, 20, 40, 80 and 160 microg) injected into SFO elicited a concentration-dependent increase in salivary secretion. L-NAME injected prior to pilocarpine into the SFO increased salivary secretion and water intake due to the effect of pilocarpine. LAR injected prior to pilocarpine into the SFO attenuated the salivary secretion and water intake. Pilocarpine, injected into the SFO increased the MAP and decreased heart rate (HR). L-NAME injected prior to pilocarpine into the SFO potentiated the pressor effect of pilocarpine with a decrease in HR. LAR injected into the SFO prior to pilocarpine attenuated the increase in MAP with no changes in HR. The present study suggests that the SFO nitrergic cells interfere in the cholinergic pathways implicated in the control of salivary secretion, fluid and cardiovascular homeostasis.
Assuntos
Homeostase/efeitos dos fármacos , Pilocarpina/farmacologia , Órgão Subfornical/efeitos dos fármacos , Animais , Arginina/administração & dosagem , Arginina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Líquidos Corporais/efeitos dos fármacos , Líquidos Corporais/fisiologia , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Agonistas Muscarínicos/farmacologia , NG-Nitroarginina Metil Éster/administração & dosagem , NG-Nitroarginina Metil Éster/farmacologia , Doadores de Óxido Nítrico/administração & dosagem , Doadores de Óxido Nítrico/farmacologia , Pilocarpina/administração & dosagem , Ratos , Saliva/efeitos dos fármacos , Salivação/efeitos dos fármacos , Órgão Subfornical/fisiologiaRESUMO
Hypothalamic paraventricular nucleus (PVN) has an important role in the regulation of water and sodium intake. Several researches described the presence of 5-HT(1) receptors in the central nervous system. 5-HT(1A) was one of the prime receptors identified and it is found in the somatodendritic and post-synaptic forms. Therefore, the aim of this study was to investigate the participation of serotonergic 5-HT(1A) receptors in the PVN on the sodium intake induced by sodium depletion followed by 24 h of deprivation (injection of the diuretic furosemide plus 24 h of sodium-deficient diet). Rats (280-320 g) were submitted to the implant of cannulas bilaterally in the PVN. 5-HT injections (10 and 20 microg/0.2 microl) in the PVN reduced NaCl 1.8% intake. 8-OH-DPAT injections (2.5 and 5.0 microg/0.2 microl) in the PVN also reduced NaCl 1.8% intake. pMPPF bilateral injections (5-HT(1A) antagonist) previously to 8-OH-DPAT injections have completely blocked the inhibitory effect over NaCl 1.8% intake. 5-HT(1A) antagonists partially reduced the inhibitory effect of 5-HT on NaCl 1.8% intake induced by sodium depletion. In contrast, the intake of palatable solution (2% sucrose) under body fluid-replete conditions was not changed after bilateral PVN 8-OH-DPTA injections. The results show that 5-HT(1A) serotonergic mechanisms in the PVN modulate sodium intake induced by sodium loss. The finding that sucrose intake was not affected by PVN 5-HT(1A) activation suggests that the effects of the 5-HT(1A) treatments on the intake of NaCl are not due to mechanisms producing a nonspecific decrease of all ingestive behaviors.
Assuntos
Núcleo Hipotalâmico Paraventricular/metabolismo , Receptor 5-HT1A de Serotonina/efeitos dos fármacos , Receptor 5-HT1A de Serotonina/metabolismo , Cloreto de Sódio na Dieta/metabolismo , 8-Hidroxi-2-(di-n-propilamino)tetralina/química , 8-Hidroxi-2-(di-n-propilamino)tetralina/metabolismo , Animais , Masculino , Núcleo Hipotalâmico Paraventricular/química , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Agonistas do Receptor de Serotonina/química , Agonistas do Receptor de Serotonina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
Calcium ions are widely accepted as critically important in responses of neurons to a stimulus. We have show previously the central involvement of angiotensin II (ANGII) in water intake. This study determined whether voltage-dependent calcium channels are involved in ANGII-induced behavioral drinking implicating nitrergic mechanism. The antidipsogenic actions of L-type calcium channel antagonists nifedipine, on ANGII-induced drinking behavior were studied when it is injected into the median preoptic nucleus (MnPO). The influence of nitric oxide (NO) on nifedipine antidipsogenic action was also studied by utilizing the N(W)-nitro-L-arginine methyl ester (L-NAME) a constitutive nitric oxide synthase inhibitor constitutive (cNOSI) and 7-nitroindazol (7-NIT) a specific neuronal nitric oxide synthase inhibitor (nNOSI) and L-arginine a NO donor. Rats 200-250 g, with cannulae implanted into MnPO, pre-treated into MnPO with either nifedipine, followed by ANGII, drank significantly less water than controls during the first 15 min after injection. However, L-NAME potentiated the dipsogenic effect of ANGII that is blocked by prior injection of nifedipine and L-arginine. 7-NIT injected prior to ANGII into MnPO also potentiated the dipsogenic effect of ANGII but with a less intensity than L-NAME that it is also blocked by prior injection of nifedipine. The results described in this paper provide evidence that calcium channels play important roles in the ANGII-induced behavioral water intake. The structures containing NO in the brain such as MnPO include both endothelial cells and neurons might be responsible for the influence of nifedipine on dipsogenic effect of ANGII. These data shows the correlation between L-type calcium channel and a free radical gas NO produced endogenously from amino acids L-arginine by endothelial and neuronal NO synthase in the control of ANGII-dipsogenic effect. This suggests that an L-type calcium channel participates in both short- and longer-term neuronal actions of ANGII by nitrergic way.
Assuntos
Angiotensina II/farmacologia , Canais de Cálcio Tipo L/fisiologia , Ingestão de Líquidos/efeitos dos fármacos , Área Pré-Óptica/efeitos dos fármacos , Animais , Cálcio/metabolismo , Indazóis/farmacologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Nifedipino/farmacologia , Óxido Nítrico/fisiologia , Área Pré-Óptica/fisiologia , RatosRESUMO
We speculated that the influence of lateral preoptic area (LPO) in sodium balance, involves arginine8-vasopressin (AVP) and angiotensin (ANG II) on Na+ uptake in LPO. Therefore, the present study investigated the effects of central administration of specific AVP and ANG II antagonists (d(CH2)5-Tyr (Me)-AVP (AAVP) and [Adamanteanacetyl1, 0-ET-d-Tyr2, Val4, Aminobutyryl6, Arg(8,9)]-AVP (ATAVP) antagonists of V1 and V2 receptors of AVP. Also the effects of losartan and CGP42112A (selective ligands of the AT1 and AT2 angiotensin receptors, respectively), was investigated on Na+ uptake and renal fluid and electrolyte excretion. After an acclimatization period of 7 days, the animals were maintained under tribromoethanol (200 mg/kg body weight, intraperitonial) anesthesia and placed in a Kopf stereotaxic instrument. Stainless guide cannula was implanted into the LPO. AAVP and ATAVP injected into the LPO prior to AVP produced a reduction in the NaCl intake. Both the AT1 and AT2 ligands administered into the LPO elicited a decrease in the NaCl intake induced by AVP injected into the LPO. AVP injection into the LPO increased sodium renal excretion, but this was reduced by prior AAVP administration. The ATAVP produced a decreased in the natriuretic effect of AVP. The losartan injected into LPO previous to AVP decreased the sodium excretion and the CGP 421122A also decreased the natriuretic effect of AVP. The AVP produced an antidiuresis effect that was inhibited by prior administration into LPO of the ATAVP. The AAVP produced no change in the antidiuretic effect of AVP. These results suggest that LPO are implicated in sodium balance that is mediated by V1, V2, AT1 and AT2 receptors.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Antagonistas de Receptores de Angiotensina , Arginina Vasopressina/antagonistas & inibidores , Receptores de Vasopressinas/administração & dosagem , Sódio/metabolismo , Angiotensina II/antagonistas & inibidores , Animais , Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/farmacologia , Arginina Vasopressina/fisiologia , Pressão Sanguínea , Relação Dose-Resposta a Droga , Hipotálamo/metabolismo , Injeções Intraventriculares , Losartan/farmacologia , Masculino , Oligopeptídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Angiotensina/fisiologiaRESUMO
We determined the effects of moxonidine and rilmenidine 20 nmol (alpha(2)-adrenergic and imidazoline receptor agonists) injected into the medial septal area (MSA) on the pilocarpine-induced salivation, when injected intraperitoneally (i.p.), of male Holtzman rats weighing 250-300 g, with stainless-steel cannula implanted into the MSA. The rats were anesthetized with zoletil 50 mg kg(-1) b.wt. (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle intramuscularly (IM), saliva was collected using pre-weighed small cotton balls inserted in the animal's mouth. The pre-treatment with moxonidine injected into the MSA reduced the salivation induced by pilocarpine (1 mg kg(-1)) injected i.p. (12+/-3 mg min(-1)) vs. control (99+/-9 mg min(-1)). The pre-treatment with rilmenidine 40 nmol also reduced the salivation induce by pilocarpine injected i.p. (20+/-5 mg min(-1)) vs. control (94+/-7 mg min(-1)). Idazoxan 40 nmol (imidazoline receptor antagonist) injected into the MSA previous to moxonidine and rilmenidine partially blocked the effect of moxonidine and totally blocked the rilmenidine effect in pilocarpine-induced salivation injected i.p. (60+/-8 and 95+/-10 mg min(-1), respectively). Yohimbine 40 nmol (alpha(2)-adrenergic receptor antagonist) injected into the MSA previously to moxonidine and rilmenidine partially blocked the moxonidine effect but produced no change on the rilmenidine effect on i.p. pilocarpine-induced salivation (70+/-6 and 24+/-6 mg min(-1), respectively). Injection of these alpha(2)-adrenergic and imidazoline agonists and antagonists agents i.p. produced no change on i.p. pilocarpine-induced salivation. These results show that central, but not peripheral, injection of alpha(2)-adrenergic and imidazoline agonists' agents inhibit pilocarpine-induced salivation. Idazoxan, an imidazoline receptor antagonist, totally inhibits the rilmenidine effect and partially inhibits the moxonidine effect on pilocarpine-induced salivation. Yohimbine produced no change on rilmenidine effect but partially inhibited the moxonidine effect. Both of these antagonists when injected into the MSA previous to pilocarpine i.p. potentiated the sialogogue effect of pilocarpine. The results suggest that alpha(2)-adrenergic/imidazoline receptor of the MSA when stimulated blocked pilocarpine-induced salivation in rats when injected intraperitonially. These receptors of the medial septal area have an inhibitory mechanism on salivary secretion.