RESUMEN
In this study, we examined whether tooth pulp stimulation (TPS) affects the stress responses in anesthetized rats. As for stress response indices, we monitored changes in the concentrations of plasma catecholamines (CAs) (adrenaline, noradrenaline, and dopamine), corticosterone (CS), and glucose (Glu). We observed that repeated TPS attenuated plasma adrenaline, dopamine, CS, and Glu levels compared with those of sham-TPS. After administering naloxone, an opioid antagonist, repeated TPS reversed the decreases in plasma CAs, CS, and Glu. These findings showed that the effects of repeated TPS may be mediated by endogenous opioid administration. Our findings suggest that repeated TPS can induce stress-analgesia and that an endogenous descending pain modulation system exists.
Asunto(s)
Glucemia/metabolismo , Catecolaminas/sangre , Corticosterona/sangre , Pulpa Dental/metabolismo , Animales , Pulpa Dental/efectos de los fármacos , Dopamina/sangre , Epinefrina/sangre , Masculino , Naloxona/farmacología , Norepinefrina/sangre , Ratas , Ratas Wistar , Estrés Fisiológico/efectos de los fármacosRESUMEN
In this study, we performed tests to determine whether tooth pulp stimulation (TPS) increases hippocampal blood flow (HBF), and if so, to investigate whether the increase in HBF is mediated via the activation of adenosine receptors. We measured HBF in urethane-anesthetized rats using laser Doppler flowmetry (LDF) and examined the effect of theophylline, a nonselective adenosine receptor antagonist, on TPS-induced HBF responses. TPS increased HBF, and its response was significantly attenuated by the intraperitoneal administration of theophylline (20 mg/kg). These results suggest that the HBF response induced by TPS may be, at least in part, produced through adenosine receptors.
Asunto(s)
Circulación Cerebrovascular/efectos de los fármacos , Cavidad Pulpar/fisiopatología , Hipocampo/efectos de los fármacos , Antagonistas de Receptores Purinérgicos P1 , Teofilina/farmacología , Odontalgia/fisiopatología , Adenosina/metabolismo , Vías Aferentes/efectos de los fármacos , Vías Aferentes/fisiología , Animales , Arterias Cerebrales/metabolismo , Circulación Cerebrovascular/fisiología , Cavidad Pulpar/inervación , Modelos Animales de Enfermedad , Estimulación Eléctrica/efectos adversos , Hipocampo/irrigación sanguínea , Hipocampo/metabolismo , Inyecciones Intraperitoneales , Flujometría por Láser-Doppler , Masculino , Nociceptores/efectos de los fármacos , Nociceptores/fisiología , Ratas , Ratas Wistar , Receptores Purinérgicos P1/metabolismo , Odontalgia/metabolismo , Vasodilatadores/farmacologíaRESUMEN
This study was designed to characterize nitric oxide (NO) production and anoxic depolarization in the rat hippocampus during transient forebrain ischemia using two NO synthase (NOS) inhibitors, L-N(5)-(1-iminoethyl)ornithine (L-NIO), a relatively selective endothelial NOS (eNOS) inhibitor, and 7-nitroindazole, a relatively selective neuronal NOS (nNOS) inhibitor, and an NO scavenger, [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide] (carboxy-PTIO). We measured the mean arterial blood pressure, hippocampal blood flow, NO concentration and direct current potential before, during and after transient forebrain ischemia, which was induced by 4-vessel occlusion for 10 min. Saline, L-NIO (20 mg/kg), 7-nitroindazole (25 mg/kg), L-NIO (20 mg/kg)+7-nitroindazole (25 mg/kg) or carboxy-PTIO (1 mg/kg) was administered intraperitoneally 20 min before the onset of ischemia. We observed early and sharp NO production in the hippocampus during ischemia in the saline group. This NO increase during ischemia was significantly reduced by L-NIO (20 mg/kg)+7-nitroindazole (25 mg/kg) or carboxy-PTIO (1 mg/kg), but not L-NIO (20 mg/kg) or 7-nitroindazole (25 mg/kg). On the other hand, NO production after ischemia was significantly reduced by 7-nitroindazole (25 mg/kg), L-NIO (20 mg/kg)+7-nitroindazole (25 mg/kg) or carboxy-PTIO (1 mg/kg), but not L-NIO (20 mg/kg). The peak latency of NO production during ischemia always preceded the onset latency of anoxic depolarization in both the saline group and the carboxy-PTIO group. In the carboxy-PTIO group, the onset latency of anoxic depolarization was significantly longer than that in the saline group. Moreover, carboxy-PTIO significantly reduced the anoxic depolarization amplitude, compared with that of the saline group. These results suggest that both NOS-dependent and-independent NO formation contributes to early and sharp NO production during ischemia, and that this NO increase is, at least in part, related to the triggering of anoxic depolarization.
Asunto(s)
Hipocampo/metabolismo , Hipocampo/fisiopatología , Hipoxia Encefálica/fisiopatología , Ataque Isquémico Transitorio/metabolismo , Ataque Isquémico Transitorio/fisiopatología , Óxido Nítrico/biosíntesis , Prosencéfalo/fisiopatología , Animales , Benzoatos/farmacología , Presión Sanguínea/efectos de los fármacos , Hipocampo/irrigación sanguínea , Imidazoles/farmacología , Indazoles/farmacología , Masculino , Microelectrodos , Óxido Nítrico Sintasa de Tipo I/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo III/antagonistas & inhibidores , Ornitina/análogos & derivados , Ornitina/farmacología , Ratas , Ratas WistarRESUMEN
To clarify whether nitric oxide (NO) modifies high K(+)-evoked gamma-aminobutyric acid (GABA) release, we examined the effects of sodium nitroprusside, an NO donor; diethyldithiocarbamate, an NO trapper; dithiothreitol, a superoxide radical scavenger; and 1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one, a specific guanylyl cyclase inhibitor, on high (100 mM) K(+)-evoked GABA release from rat hippocampus in vivo using microdialysis. Perfusion with 0.5 or 5 mM sodium nitroprusside significantly reduced high K(+)-evoked GABA release. Co-perfusion with 0.5 mM sodium nitroprusside and 5 mM diethyldithiocarbamate or 0.5 mM 1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one significantly enhanced high K(+)-evoked GABA release. Co-perfusion with 0.5 mM sodium nitroprusside and 1 mM dithiothreitol tended to increase it. These results demonstrate that sodium nitroprusside reduces high K(+)-evoked GABA release both via an NO/cyclic GMP-dependent pathway and via an NO-dependent, but cyclic GMP-independent, pathway in rat hippocampus in vivo.
Asunto(s)
Hipocampo/metabolismo , Donantes de Óxido Nítrico/farmacología , Óxido Nítrico/fisiología , Nitroprusiato/farmacología , Potasio/farmacología , Ácido gamma-Aminobutírico/metabolismo , Animales , Ditiotreitol/farmacología , Ditiocarba/farmacología , Depuradores de Radicales Libres/farmacología , Guanilato Ciclasa/antagonistas & inhibidores , Hipocampo/efectos de los fármacos , Masculino , Microdiálisis , Oxadiazoles/farmacología , Quinoxalinas/farmacología , Ratas , Ratas WistarRESUMEN
The present study investigated the effects of (-)-epigallocatechin gallate (EGCG), which is the major component of polyphenol in green tea, on nitric oxide (NO) stress-induced neuronal damage, by monitoring NO mobilizations in the intact rat hippocampus and assaying the viability of cultured rat hippocampal neurons. A 10-min ischemia increased NO (NO(3)(-)/NO(2)(-)) concentrations in the intact rat hippocampus, while EGCG (50 mg/kg i.p.) inhibited the increase by 77% without affecting hippocampal blood flow. The NO donor, sodium nitroprusside (SNP; 50 microM), produced NO (NO(3)(-)/NO(2)(-)), while EGCG inhibited it in a dose-dependent manner at concentrations ranging from 50 to 200 microM. Treatment with SNP (100 microM) reduced the viability of cultured rat hippocampal neurons to 22% of control levels, while EGCG caused it to recover to 51% for 10 microM, 73% for 20 microM, and 70% for 50 microM. Taken together, it appears that EGCG could protect against ischemic neuronal damage by deoxidizing peroxynitrate/peroxynitrite, which is converted to NO radical or hydroxy radical.
Asunto(s)
Antioxidantes/farmacología , Isquemia Encefálica/tratamiento farmacológico , Catequina/análogos & derivados , Catequina/farmacología , Hipocampo/efectos de los fármacos , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Óxido Nítrico/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Animales , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Circulación Cerebrovascular/efectos de los fármacos , Hipocampo/metabolismo , Neuronas/metabolismo , Donantes de Óxido Nítrico/farmacología , Nitroprusiato/farmacología , Ratas , Ratas WistarRESUMEN
To clarify the functions of nitric oxide (NO) induced by either neuronal NO synthase (nNOS) or endothelial NO synthase (eNOS) after transient cerebral ischemia, we investigated the effects of L-N(5)-(1-iminoethyl)ornithine (L-NIO), a relatively selective eNOS inhibitor, and 7-nitroindazole (7-NI), a relatively selective nNOS inhibitor, on hippocampal dysfunction caused by cerebral ischemia. We measured mean arterial blood pressure (MABP), hippocampal blood flow, direct current (DC) potential, CA1 population spike (PS) and extracellular concentrations of glutamate from rat hippocampus after transient forebrain ischemia, which was induced by four-vessel occlusion for 10 min. L-NIO (20 mg/kg) and 7-NI (25 mg/kg) were administered intraperitoneally 20 min before ischemia. L-NIO, but not 7-NI, increased MABP before, during and after ischemia, compared with the vehicle group. 7-NI, but not L-NIO, reduced the amplitude of anoxic depolarization induced by ischemia. 7-NI recovered the PS amplitude in part 60 min after ischemia. 7-NI, but not L-NIO, reduced the ischemia-induced levels of glutamate. These results indicate that nNOS inhibition with 7-NI improves, at least in part, hippocampal dysfunction after ischemia, while eNOS inhibition with L-NIO worsens it.