RESUMEN
Several findings suggest that catecholaminergic neurons in the caudal ventrolateral medulla (CVLM) contribute to body fluid homeostasis and cardiovascular regulation. From the CVLM other areas in central nervous system involved in cardiovascular regulation and hydroelectrolyte balance can be activated. Therefore, the aim of the present study was to investigate the effects of lesions of these neurons on 0.3M NaCl and water intake induced by subcutaneous injection of furosemide (FURO)+captopril (CAP) or 36 h of water deprivation/partial hydration with only water (WD/PR). Male Wistar rats (320-360 g) were submitted to medullary catecholaminergic neuron lesions by microinjection of anti-dopamine-beta-hydroxylase-saporin (anti-DbetaH-saporin; 6.3 ng in 60 nl) into the CVLM (SAP-rats). Sham rats received microinjections of free saporin (1.3 ng in 60 nl) in the same region. In SAP-rats, the 0.3M NaCl intake was increased after FURO+CAP (6.8+/-1.0 ml/2h, vs. sham: 3.7+/-0.7 ml/2h) as well as after WD/PR (11.1+/-1.3 ml/2h vs. sham: 6.1+/-1.8 ml/2h). Conversely, in SAP-rats, the water intake induced by FURO+CAP (14.8+/-1.3 ml/2h, vs. sham: 14.1+/-1.6 ml/2h) or by WD/PR (3.6+/-0.9 ml/2h, vs. sham: 3.2+/-1.1 ml/2h) was not different from sham rats. Immunohistochemical analysis indicates that microinjections of anti-DbetaH-saporin produced extensive destruction within the A1 cell groups in the CVLM. These results suggest an inhibitory role for medullary catecholaminergic neurons on sodium appetite.
Asunto(s)
Catecolaminas/metabolismo , Bulbo Raquídeo/metabolismo , Neuronas/metabolismo , Cloruro de Sodio/metabolismo , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/metabolismo , Regulación del Apetito/efectos de los fármacos , Captopril/administración & dosificación , Captopril/farmacología , Dopamina beta-Hidroxilasa/antagonistas & inhibidores , Ingestión de Líquidos/efectos de los fármacos , Combinación de Medicamentos , Furosemida/administración & dosificación , Furosemida/farmacología , Inmunohistoquímica , Inyecciones Subcutáneas , Masculino , Bulbo Raquídeo/efectos de los fármacos , Bulbo Raquídeo/patología , Microinyecciones/métodos , Neuronas/efectos de los fármacos , Neuronas/patología , Ratas , Ratas Wistar , Proteínas Inactivadoras de Ribosomas Tipo 1/administración & dosificación , Proteínas Inactivadoras de Ribosomas Tipo 1/metabolismo , Proteínas Inactivadoras de Ribosomas Tipo 1/toxicidad , Saporinas , Cloruro de Sodio/administración & dosificación , Privación de AguaRESUMEN
The acute and chronic effects of a potent selective dopamine beta-hydroxylase inhibitor, SK&F 102698, were assessed in chronically instrumented 1-kidney, 1-clip Goldblatt hypertensive dogs. Blood pressure measured directly from either a carotid loop or from a vascular access port and cardiac output measured by impedence cardiography were monitored following acute (30 and 100 mg/kg, p.o.) and chronic (30 mg/kg/day for 4 days) administration of SK&F 102698. The data indicate that SK&F 102698 failed to alter blood pressure, cardiac output or total peripheral resistance after either acute or chronic administration. It is concluded that dopamine beta-hydroxylase inhibition with SK&F 102698 is not an effective antihypertensive agent in the 1-kidney, 1-clip Goldblatt hypertensive dog model.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Dopamina beta-Hidroxilasa/antagonistas & inhibidores , Hipertensión Renovascular/fisiopatología , Imidazoles/farmacología , Animales , Gasto Cardíaco/efectos de los fármacos , Perros , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Volumen Sistólico/efectos de los fármacos , Resistencia Vascular/efectos de los fármacosRESUMEN
The acute and chronic effects of a potent and selective dopamine beta-hydroxylase inhibitor, SK&F 102698 [1-(3,5-difluorobenzyl)imidazole-2-thiol], on systemic hemodynamic variables were assessed in chronically instrumented spontaneously hypertensive and normotensive Wistar rats. The changes observed in the hypertensive rats were compared with those obtained by vehicle in a different group of rats. Following intragastric administration of SK&F 102698 (75 mg/kg), blood pressure and cardiac output decreased gradually in both strains of rats, while total peripheral vascular resistance remained unchanged. The antihypertensive effect of repeated daily administration of SK&F 102698 in the hypertensive rats was sustained for the duration of treatment. During the acute phase, the decrease in cardiac output was due to bradycardia. In addition, as a result of hemodynamic changes, SK&F 102698 significantly reduced the minute work output of the heart. The results indicate that SK&F 102698 lowers blood pressure primarily by decreasing cardiac output.