RESUMEN
Albuminuria and increased regional albumin clearance are known to develop concomitantly in diabetes. The anti-proteinuric effect of angiotensin-converting enzyme inhibitor therapy is well established. We studied whether angiotensin-converting enzyme inhibitor therapy with perindoprilat in comparison with conventional antihypertensive treatment could influence the development of increased regional albumin clearance as well as albuminuria in experimental diabetes. Rats with streptozotocin-induced diabetes were randomized into a saline group (n = 7), a perindoprilat (1 mg/kg per day) group (n = 8), and a hydralazine (3 mg/kg per day) group (n = 6); six rats served as non-diabetic controls. After 6-8 weeks, blood pressure was equally reduced in the perindoprilat- and hydralazine-treated groups (P < 0.01). Twenty-four-hour urinary protein and albumin excretion were increased in diabetic rats compared to control rats (P < 0.001). Hydralazine did not reduce 24 h protein or albumin excretion, whereas perindoprilat treatment reduced both (P < 0.001) to levels comparable to those of control rats. Regional albumin clearance, assessed in the eye, ileum, lung, skeletal muscle and skin, was clearly elevated in diabetic rats compared to control rats; however, neither drug therapy had an effect on albumin clearance.
Asunto(s)
Albúminas/metabolismo , Albuminuria/tratamiento farmacológico , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Permeabilidad Capilar/efectos de los fármacos , Diabetes Mellitus Experimental/fisiopatología , Indoles/farmacología , Albuminuria/metabolismo , Animales , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Experimental/orina , Hidralazina/farmacología , Masculino , Distribución Aleatoria , Ratas , Ratas WistarAsunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Hipotálamo Anterior/fisiología , Imidazoles/farmacología , Receptores Adrenérgicos alfa/fisiología , Animales , Hipotálamo Anterior/efectos de los fármacos , Masculino , Ratas , Receptores Adrenérgicos alfa/efectos de los fármacos , Técnicas EstereotáxicasAsunto(s)
Agonistas alfa-Adrenérgicos , Imidazoles/farmacología , Animales , Sitios de Unión , Presión Sanguínea , Clonidina/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Imidazoles/metabolismo , Técnicas In Vitro , Yeyuno/efectos de los fármacos , Masculino , Conejos , Ratas , Receptores Adrenérgicos , Relación Estructura-ActividadRESUMEN
1. Various drugs were injected stereotactically into the brain of anaesthetized rats. 2. Noradrenaline injected into the area of the nucleus of the tractus solitarius in the lower brain stem or into the far anterior hypothalamus/pre-optic region induced a fall in blood pressure and heart rate related to the administered dose. 3. When injected into the anterior hypothalamus/pre-optic region, clonidine and alpha-methylnoradrenaline induced a long-lasting decrease in blood pressure and heart rate.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Encéfalo/fisiología , Receptores Adrenérgicos alfa/fisiología , Receptores Adrenérgicos/fisiología , Animales , Clonidina/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Hipotálamo , Inyecciones , Masculino , Metildopa/administración & dosificación , Norepinefrina/administración & dosificación , Ratas , Técnicas EstereotáxicasRESUMEN
Noradrenaline (NA) induced a decrease in blood pressure and heart rate when injected into specific areas in either the medulla oblongata or the hypothalamus. In the medulla the area of the nucleus tractus solitarius was specifically sensitive to NA; in the hypothalamus depressor effects were obtained only after NA injections into the anterior hypothalamic/preoptic region. The cardiovascular effects induced by NA (3-40 nmol) in these areas consisted of an immediate decrease in both arterial pressure and heart rate. Size and duration of these effects depended upon the dose of NA injected. Alpha-methylNA (5-15 nmol) induced a long lasting decrease in blood pressure and heart rate when injected into the anterior hypothalamic/preoptic region. These data are discussed in view of the existence of at least two sites within the central nervous system (CNS) from which interference with noradrenergic mechanisms can cause changes in the cardiovascular system.