RESUMO
Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for ß-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.
Assuntos
Tecido Adiposo Marrom/metabolismo , Antagonistas Adrenérgicos beta/administração & dosagem , Iodeto Peroxidase/metabolismo , Infarto do Miocárdio/metabolismo , Propranolol/administração & dosagem , Tiroxina/sangue , Tri-Iodotironina/sangue , Tecido Adiposo Marrom/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Iodeto Peroxidase/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Tiroxina/efeitos dos fármacos , Tri-Iodotironina/efeitos dos fármacos , Iodotironina Desiodinase Tipo IIRESUMO
Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for β-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.
Assuntos
Animais , Masculino , Ratos , Propranolol/administração & dosagem , Tiroxina/sangue , Tecido Adiposo Marrom/metabolismo , Agonistas Adrenérgicos beta/administração & dosagem , Iodeto Peroxidase/metabolismo , Infarto do Miocárdio/metabolismo , Tiroxina/efeitos dos fármacos , Tri-Iodotironina/efeitos dos fármacos , Tri-Iodotironina/sangue , Tecido Adiposo Marrom/efeitos dos fármacos , Ratos Wistar , Modelos Animais de Doenças , Iodeto Peroxidase/efeitos dos fármacosRESUMO
1. Recently, we demonstrated that oral captopril treatment improved diastolic function and attenuated cardiac remodelling after myocardial infarction (MI) in rats. Considering the feasible role of the brain renin-angiotensin system (RAS) in heart failure, in the present study we investigated the role of the captopril injected intracerebroventricularly (i.c.v.) on the progression of cardiac dysfunction. 2. Male Wistar rats underwent experimental MI or sham operation. Infarcted animals received daily i.c.v. injections of captopril (approximately 200 mg/kg; MI + Cap) or saline (MI) from 11 to 18 days after infarction. Electro- and echocardiogram assessments were performed before and after i.c.v. treatment (10 and 18 days after MI, respectively). Water and hypertonic saline ingestion were determined daily between 12 and 16 days after MI. 3. Electrocardiograms from the MI and MI + Cap groups showed signs that resembled large MI before and after i.c.v. treatment. However, despite similar systolic dysfunction observed in both groups, only captopril-treated rats exhibited reduced left ventricular (LV) dilatation and improved LV filling, as assessed by echocardiograms, and low levels of water ingestion compared with the saline-treated control group. 4. The results of the present study suggest that the brain RAS may participate in the development of cardiac dysfunction induced by ischaemia and that inhibition of the brain RAS may provide a new strategy for the prevention of diastolic dysfunction.
Assuntos
Encéfalo/metabolismo , Diástole/efeitos dos fármacos , Infarto do Miocárdio/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Encéfalo/efeitos dos fármacos , Captopril/administração & dosagem , Captopril/farmacologia , Captopril/uso terapêutico , Modelos Animais de Doenças , Ecocardiografia , Eletrocardiografia , Injeções Intraventriculares , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Ratos , Ratos WistarRESUMO
The purpose of this study was to explore the role of L-5-hydroxytryptophan (L-HTP) and its relationship with the renin-angiotensin system (RAS) on the drinking behavior in Japanese quails. Normally-hydrated quails that received injections of L-HTP (12.5; 25 and 50 mg.kg-1) by the intracoelomic route (ic) expressed an increase in water intake, which was inhibited by captopril, an angiotensin converting enzyme (ACE) inhibitor. In addition, captopril also induced such a response in birds under previous fluid deprivation. High doses of captopril (35-70 mg.kg-1, sc) in normally-hydrated quails decreased the spontaneous water intake while low doses of captopril (2-5 mg.kg-1, sc) did not prompt water intake after L-HTP administration. Losartan, an AT1 receptor antagonist in mammals, did not change the water intake levels in normally-hydrated or water-deprivated birds. Serotonin (5-HT) injections did not provoke its known dipsogenic response.
O objetivo deste estudo foi investigar a influência do L-5-hidroxitriptofano (L-HTP) e sua relação com o sistema renina-angiotensina (SRA) no comportamento dipsogênico de codornas. Codornas normohidratadas que receberam L-HTP em diferentes doses (12,5; 25 e 50 mg.kg-1) por via intracelomática (ic) expressaram um aumento na ingestão de água, o qual foi suprimido pela administração prévia de captopril (inibidor da ECA-enzima conversora de angiotensina). Esta ação inibitória do captopril, em menor intensidade, foi também evidenciada em aves previamente submetidas ao jejum hídrico. O tratamento isolado com captopril (35-70 mg.kg-1) reduziu consideravelmente a ingestão espontânea de água em codornas normohidratadas, enquanto baixas doses (2-5 mg.kg-1) não provocaram aumento na ingestão de água induzida pelo L-HTP. Losartan, um antagonista de receptores AT1 em mamíferos, não foi capaz de modificar os níveis de ingestão hídrica, tanto em aves normohidratadas quanto em aves privadas de água. Serotonina aplicada perifericamente não promoveu a conhecida resposta dipsogênica de mamíferos.
Assuntos
Animais , Masculino , /farmacologia , Coturnix/fisiologia , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Sistema Renina-Angiotensina/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Comportamento de Ingestão de Líquido/fisiologia , Sistema Renina-Angiotensina/fisiologia , Fatores de TempoRESUMO
This study aimed to demonstrate the influence of the systemic administration of l-5-hydroxy-tryptophan (L-HTP) on the plasma levels of melatonin during the dark period in quails. Throughout daylight, the plasma levels of melatonin did not differ significantly, oscillating between 110.2 +/- 15.8 pg.mL(-1) and 157.4 +/- 34.8 pg.mL(-1), from 8 to 16 hours. L-HTP (25 mg.kg(-1), through the intracelomic route) administered at 18 hours lessened significantly the nocturnal increase of the plasma levels of melatonin (controls, 327.3 +/- 20.1 and 315.8 +/- 20.9 pg.mL(-1) vs. 242.1 +/- 24.8 and 217.5 +/- 21 pg.mL(-1), respectively, at 20 and 24 hours, P < 0.05). The results obtained showed that the administration of LHTP reduced the nocturnal melatonin release, possibly by bringing about an increase in serotonin synthesis and synaptic release in the pineal. Therefore, the serotoninergic transmission from the raphe towards the pineal would constitute a mechanism of modulation of the synthesis and melatonin release in quails.
Assuntos
5-Hidroxitriptofano/farmacologia , Ritmo Circadiano , Coturnix/sangue , Melatonina/sangue , Glândula Pineal/efeitos dos fármacos , Animais , Glândula Pineal/metabolismo , RadioimunoensaioRESUMO
The present study was carried out to assess the influence of noradrenergic stimulation of the midbrain dorsal (DRN) and median raphe nuclei (MRN) on urinary volume and electrolyte excretion in hydrated rats. Wistar rats were implanted with a guide cannula into the MRN or DRN and then submitted to two intragastric administrations of water in order to attain an increased diuresis. The following treatments were performed. (1) Intra-DRN microinjections of saline (0.2 microl), alpha(1)-adrenergic agonist phenylephrine (PHE, 0.49 and 4.9 nmol in 0.2 microl), alpha(2)-adrenergic antagonist idazoxan (IDZ, 0.42 and 4.2 nmol in 0.2 microl) or the alpha(1)-adrenergic antagonist prazosin (PRZ, 0.24 and 2.4 nmol in 0.2 microl). (2) Intra-MRN microinjections of saline, IDZ (4.2 nmol in 0.2 microl), PHE (4.9 nmol in 0.2 microl) or PRZ (2.4 nmol in 0.2 microl). Urine samples were subsequently collected over 120 min at 20 min intervals for photometric measurement of sodium and potassium. Intra-DRN administration of PHE and IDZ significantly increased the urinary volume, natriuresis and kaliuresis. Intra-DRN microinjection of a higher dose of PRZ reduced the urinary volume and both sodium and potassium excretion. Intra-MRN microinjections of PHE, IDZ or PRZ did not induce any significant effect on urinary volume or electrolyte excretion. These data suggest that the increase of tonic excitatory noradrenergic input conveyed to DRN influences the hydroelectrolyte homeostasis, possibly through 5-HTergic circuitry.
Assuntos
Norepinefrina/fisiologia , Potássio/urina , Núcleos da Rafe/fisiologia , Sódio/urina , Equilíbrio Hidroeletrolítico/fisiologia , Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Diurese/efeitos dos fármacos , Diurese/fisiologia , Ingestão de Líquidos/fisiologia , Idazoxano/farmacologia , Masculino , Microinjeções , Natriurese/efeitos dos fármacos , Natriurese/fisiologia , Fenilefrina/farmacologia , Prazosina/farmacologia , Núcleos da Rafe/efeitos dos fármacos , Ratos , Ratos Wistar , Urina , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
This study was carried out aiming to reach behavioral and neuropharmacological evidence of the permeability of the blood-brain barrier (BBB) to serotonin systemically administered in quails. Serotonin injected by a parenteral route (250-1000 microg x kg(-1), sc) elicited a sequence of behavioral events concerned with a sleeping-like state. Sleeping-like behaviors began with feather bristling, rapid oral movements, blinking and finally crouching and closure of the eyes. Previous administration of 5-HT2C antagonist, LY53857 (3 mg x kg(-1), sc) reduced the episodes of feather bristling and rapid oral movements significantly but without altering the frequency of blinking and closure of the eyes. Treatment with the 5-HT2A/2C antagonist, ketanserin (3 mg x kg(-1), sc) did not affect any of the responses evoked by the serotonin. Quipazine (5 mg x kg(-1), sc) a 5-HT2A/2C/3 agonist induced intense hypomotility, long periods of yawning-like and sleeping-like states. Previous ketanserin suppressed gaping responses and reduced hypomotility, rapid oral movements and bristling but was ineffective for remaining responses induced by quipazine. Results showed that unlike mammals, serotonin permeates the BBB and activates hypnogenic mechanisms in quails. Studies using serotoninergic agonist and antagonists have disclosed that among the actions of the serotonin, feather bristling, rapid oral movements and yawning-like state originated from activation of 5-HT2 receptors while blinking and closure of the eyes possibly require other subtypes of receptors.
Assuntos
Barreira Hematoencefálica/metabolismo , Serotonina/farmacocinética , Sono/efeitos dos fármacos , Bocejo/efeitos dos fármacos , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Coturnix , Relação Dose-Resposta a Droga , Ketanserina/farmacologia , Masculino , Quipazina/farmacologia , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologiaRESUMO
This study aimed to demonstrate the influence of the systemic administration of l-5-hydroxy-tryptophan (L-HTP) on the plasma levels of melatonin during the dark period in quails. Throughout daylight, the plasma levels of melatonin did not differ significantly, oscillating between 110.2 ± 15.8 pg.mL-1 and 157.4 ± 34.8 pg.mL-1, from 8 to 16 hours. L-HTP (25 mg.kg-1, through the intracelomic route) administered at 18 hours lessened significantly the nocturnal increase of the plasma levels of melatonin (controls, 327.3 ± 20.1 and 315.8 ± 20.9 pg.mL-1 vs. 242.1 ± 24.8 and 217.5 ± 21 pg.mL-1, respectively, at 20 and 24 hours, P < 0.05). The results obtained showed that the administration of LHTP reduced the nocturnal melatonin release, possibly by bringing about an increase in serotonin synthesis and synaptic release in the pineal. Therefore, the serotoninergic transmission from the raphe towards the pineal would constitute a mechanism of modulation of the synthesis and melatonin release in quails.
Este trabalho objetivou demonstrar a influência da administração sistêmica de l-5-hidroxi-triptofano (L-HTP) sobre os níveis plasmáticos de melatonina durante o período noturno em codornas. Ao longo do período claro, os níveis plasmáticos de melatonina não diferiram significativamente, oscilando entre 110,2 ± 15,8 pg.mL-1 e 157,4 ± 34,8 pg.mL-1, de 8 às 16 horas. L-HTP (25 mg.kg-1, via intracelomática), administrado às 18 horas atenuou significativamente a elevação noturna dos níveis plasmáticos de melatonina (controles, 327,3 ± 20,1 e 315,8 ± 20,9 pg.mL-1 vs. 242,1 ± 24,8 e 217,5 ± 21 pg.mL-1, respectivamente, às 20 e 24 horas, P < 0,05). Os resultados obtidos mostraram que a administração de L-HTP reduziu a liberação noturna de melatonina, possivelmente por suscitar um aumento da síntese e liberação sináptica de serotonina na pineal. Portanto, a transmissão serotoninérgica da rafe para a pineal constituiria um mecanismo de modulação da síntese e/ou liberação de melatonina em codornas.
Assuntos
Animais , /farmacologia , Ritmo Circadiano , Melatonina/metabolismo , Serotonina/análogos & derivados , CoturnixRESUMO
This study was carried out aiming to reach behavioral and neuropharmacological evidence of the permeability of the blood-brain barrier (BBB) to serotonin systemically administered in quails. Serotonin injected by a parenteral route (250-1000 æg.kg-1, sc) elicited a sequence of behavioral events concerned with a sleeping-like state. Sleeping-like behaviors began with feather bristling, rapid oral movements, blinking and finally crouching and closure of the eyes. Previous administration of 5-HT2C antagonist, LY53857 (3 mg.kg-1, sc) reduced the episodes of feather bristling and rapid oral movements significantly but without altering the frequency of blinking and closure of the eyes. Treatment with the 5-HT2A/2C antagonist, ketanserin (3 mg.kg-1, sc) did not affect any of the responses evoked by the serotonin. Quipazine (5 mg.kg-1, sc) a 5-HT2A/2C/3 agonist induced intense hypomotility, long periods of yawning-like and sleeping-like states. Previous ketanserin suppressed gaping responses and reduced hypomotility, rapid oral movements and bristling but was ineffective for remaining responses induced by quipazine. Results showed that unlike mammals, serotonin permeates the BBB and activates hypnogenic mechanisms in quails. Studies using serotoninergic agonist and antagonists have disclosed that among the actions of the serotonin, feather bristling, rapid oral movements and yawning-like state originated from activation of 5-HT2 receptors while blinking and closure of the eyes possibly require other subtypes of receptors.
Este estudo foi desenvolvido objetivando ampliar as evidências comportamentais e neurofarmacológicas da permeabilidade da barreira hematoencefálica (BHE) à serotonina administrada sistemicamente em codornas. A serotonina injetada por via parenteral (250-1000 æg.kg-1, sc) produziu uma seqüência de eventos relacionados com um estado semelhante ao sono. Comportamentos semelhantes ao sono começaram com o eriçamento das penas, movimentos orais rápidos, piscadelas e finalmente agachamento e fechamento dos olhos. A administração prévia do antagonista do receptor 5-HT2C, LY53857 (3 mg.kg-1, sc) reduziu significativamente os episódios de eriçamento das penas e movimentos orais rápidos, mas não alterou a freqüência de piscadelas e fechamento dos olhos. Tratamento com o antagonista do receptor 5-HT2A/2C, quetanserina (3 mg.kg-1, sc) não afetou nenhuma das respostas evocadas pela serotonina. A quipazina (5 mg.kg-1, sc), um agonista dos receptores 5-HT2A/2C/3, induziu intensa hipomotilidade e longos períodos de comportamentos semelhantes ao bocejo e ao sono. O tratamento prévio com quetanserina suprimiu as reações de bocejo e reduziu a hipomotilidade, os movimentos orais rápidos e as piscadelas, mas foi sem efeito para as demais respostas induzidas pela quipazina. Os resultados mostraram que, diferentemente dos mamíferos, a serotonina atravessa a BHE e ativa mecanismos hipnogênicos em codornas. Estudos com agonistas serotoninérgicos e antagonistas revelaram que, entre as ações da serotonina, o eriçamento das penas, os movimentos orais rápidos e o comportamento semelhante ao bocejo foram originados pela ativação de receptores 5-HT2, enquanto o piscar e o fechamento dos olhos possivelmente requereu outros subtipos de receptores.
Assuntos
Animais , Masculino , Comportamento Animal/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Serotonina/farmacocinética , Sono/efeitos dos fármacos , Bocejo/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Coturnix , Relação Dose-Resposta a Droga , Ketanserina/farmacologia , Quipazina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Antagonistas da Serotonina/farmacologiaRESUMO
The purpose of this study was to explore the role of L-5-hydroxytryptophan (L-HTP) and its relationship with the renin-angiotensin system (RAS) on the drinking behavior in Japanese quails. Normally-hydrated quails that received injections of L-HTP (12.5; 25 and 50 mg.kg-1) by the intracoelomic route (ic) expressed an increase in water intake, which was inhibited by captopril, an angiotensin converting enzyme (ACE) inhibitor. In addition, captopril also induced such a response in birds under previous fluid deprivation. High doses of captopril (35-70 mg.kg-1, sc) in normally-hydrated quails decreased the spontaneous water intake while low doses of captopril (2-5 mg.kg-1, sc) did not prompt water intake after L-HTP administration. Losartan, an AT1 receptor antagonist in mammals, did not change the water intake levels in normally-hydrated or water-deprivated birds. Serotonin (5-HT) injections did not provoke its known dipsogenic response.