RESUMEN
Central cholinergic activation stimulates water intake, but also NaCl intake when the inhibitory mechanisms are blocked with injections of moxonidine (α2 adrenergic/imidazoline agonist) into the lateral parabrachial nucleus (LPBN). In the present study, we investigated the involvement of central M1 and M2 muscarinic receptors on NaCl intake induced by pilocarpine (non-selective muscarinic agonist) intraperitoneally combined with moxonidine into the LPBN or by muscimol (GABAA agonist) into the LPBN. Male Holtzman rats with stainless steel cannulas implanted bilaterally in the LPBN and in the lateral ventricle were used. Pirenzepine (M1 muscarinic antagonist, 1 nmol/1 µl) or methoctramine (M2 muscarinic antagonist, 50 nmol/1 µL) injected intracerebroventricularly (i.c.v.) reduced 0.3 M NaCl and water intake in rats treated with pilocarpine (0.1 mg/100 g of body weight) injected intraperitoneally combined with moxonidine (0.5 nmol/0.2 µL) into the LPBN. In rats treated with muscimol (0.5 nmol/0.2 µL) into the LPBN, methoctramine i.c.v. also reduced 0.3 M NaCl and water intake, however, pirenzepine produced no effect. The results suggest that M1 and M2 muscarinic receptors activate central pathways involved in the control of water and sodium intake that are under the influence of the LPBN inhibitory mechanisms.
Asunto(s)
Ingestión de Líquidos/efectos de los fármacos , Núcleos Parabraquiales/metabolismo , Receptor Muscarínico M1/metabolismo , Receptor Muscarínico M2/metabolismo , Cloruro de Sodio/metabolismo , Animales , Diaminas/farmacología , Conducta de Ingestión de Líquido/efectos de los fármacos , Imidazoles/farmacología , Masculino , Agonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/farmacología , Muscimol/farmacología , Núcleos Parabraquiales/efectos de los fármacos , Pilocarpina/farmacología , Pirenzepina/farmacología , Ratas , Ratas Sprague-Dawley , Receptor Muscarínico M1/efectos de los fármacos , Receptor Muscarínico M2/efectos de los fármacos , Sodio en la DietaRESUMEN
The knowledge of the mechanisms underlying circulating volume control may be achieved by stretching a balloon placed at the junction of the superior vena cava-right atrial junction (SVC-RAJ). We investigated whether the inflation of a balloon at the SVC-RAJ inhibits the intake of 0.3M NaCl induced by GABAA receptor activation in the lateral parabrachial nucleus (LPBN) in euhydrated and satiated rats. Male Wistar rats (280-300 g) with bilateral stainless steel LPBN cannulae and balloons implanted at the SVC-RAJ were used. Bilateral injections of the GABAA receptor agonist muscimol (0.5 ηmol/0.2l) in the LPBN with deflated balloons increased intake of 0.3M NaCl (30.1 ± 3.9 vs. saline: 2.2 ± 0.7)ml/210 min, n=8) and water (17.7 ± 1.9 vs. saline: 2.9 ± 0.5 ml/210 min). Conversely, 0.3M NaCl (27.8 ± 2.1 ml/210 min) and water (22.8 ± 2.3 ml/210 min) intake were not affected in rats with inflated balloons at the SVC-RAJ. The results show that sodium and water intake induced by muscimol injected into the LPBN was not affected by balloon inflation at the SVC-RAJ. We suggest that the blockade of LPBN neuronal activity with muscimol injections impairs inhibitory mechanisms activated by signals from cardiopulmonary volume receptors determined by balloon inflation.
Asunto(s)
Agonistas de Receptores de GABA-A/farmacología , Corazón/fisiopatología , Muscimol/farmacología , Puente/metabolismo , Receptores de GABA-A/metabolismo , Cloruro de Sodio/metabolismo , Animales , Cateterismo , Ingestión de Líquidos , Corazón/efectos de los fármacos , Atrios Cardíacos/fisiopatología , Masculino , Ratas Wistar , Cloruro de Sodio/administración & dosificación , Vena Cava Superior/fisiopatologíaRESUMEN
A prospective study of 55 confirmed or presumptive cases of cerebral toxoplasmosis in HIV positive patients in Brazil was performed to describe clinical characteristics and to identify predictive factors for clinical response to the anti-Toxoplasma treatment. Cerebral toxoplasmosis led to the diagnosis of HIV infection in 19 (35%) patients, whereas it was the AIDS defining disease in 41 (75%) patients. Of these, 22 (54%) patients were previously know to be HIV-positive. At diagnosis of cerebral toxoplasmosis, only 4 (7%) patients were on highly active antiretroviral therapy (HAART), and 6 (11%) were receiving primary cerebral toxoplasmosis prophylaxis. The mean CD4+ cell count was 64.2 (+/- 69.1) cells per microliter. Forty-nine patients (78%) showed alterations consistent with toxoplasmosis on brain computed tomography. At 6 weeks of treatment, 23 (42%) patients had complete clinical response, 25 (46%) partial response, and 7 (13%) died. Alteration of consciousness, Karnofsky score less than 70, psychomotor slowing, hemoglobin less than 12 mg/dL, mental confusion, Glasgow Coma Scale less than 12 were the main predictors of partial clinical response. All patients were placed on HAART within the first 4 weeks of diagnosis of cerebral toxoplasmosis. One year after the diagnosis, all available patients were on HAART and toxoplasmosis prophylaxis, and only 2 patients had relapse of cerebral toxoplasmosis. In Brazilian patients with AIDS, cerebral toxoplasmosis mainly occurs as an AIDS-defining disease, and causes significant morbidity and mortality. Signs of neurologic deterioration predict an unfavorable response to the treatment. Early start of HAART seems to be related to better survival and less relapses.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA , Seropositividad para VIH/complicaciones , Toxoplasmosis Cerebral , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/parasitología , Infecciones Oportunistas Relacionadas con el SIDA/fisiopatología , Infecciones Oportunistas Relacionadas con el SIDA/prevención & control , Adulto , Antiprotozoarios/uso terapéutico , Terapia Antirretroviral Altamente Activa , Brasil , Femenino , Seropositividad para VIH/tratamiento farmacológico , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Toxoplasmosis Cerebral/diagnóstico , Toxoplasmosis Cerebral/parasitología , Toxoplasmosis Cerebral/fisiopatología , Toxoplasmosis Cerebral/prevención & control , Resultado del TratamientoRESUMEN
Central cholinergic mechanisms are suggested to participate in osmoreceptor-induced water intake. Therefore, central injections of the cholinergic agonist carbachol usually produce water intake (i.e., thirst) and are ineffective in inducing the intake of hypertonic saline solutions (i.e., the operational definition of sodium appetite). Recent studies have indicated that bilateral injections of the serotonin receptor antagonist methysergide into the lateral parabrachial nucleus (LPBN) markedly increases salt intake in models involving the activation of the renin-angiotensin system or mineralocorticoid hormones. The present studies investigated whether sodium appetite could be induced by central cholinergic activation with carbachol (an experimental condition where only water is typically ingested) after the blockade of LPBN serotonergic mechanisms with methysergide treatment in rats. When administered intracerebroventricularly in combination with injections of vehicle into both LPBN, carbachol (4 nmol) caused water drinking but insignificant intake of hypertonic saline. In contrast, after bilateral LPBN injections of methysergide (4 microg), intracerebroventricular carbachol induced the intake of 0.3 M NaCl. Water intake stimulated by intracerebroventricular carbachol was not changed by LPBN methysergide injections. The results indicate that central cholinergic activation can induce marked intake of hypertonic NaCl if the inhibitory serotonergic mechanisms of the LPBN are attenuated.