RESUMEN
1. The studies were designed to investigate the changes in responsiveness to beta-adrenoceptor agonists induced by chronic administration of beta-adrenoceptor antagonists and agonists. 2. Dose-response curves for dopexamine, isoprenaline, noradrenaline and impromidine on heart rate, blood pressure and myocardial contractility (dP/dt:integrated isometric tension) were obtained in untreated dogs and compared to those measured in dogs which had been pretreated with propranolol (8 mg kg-1 day-1), atenolol (6 mg kg-1 day-1), isoprenaline (0.5 microgram kg-1 min-1) or noradrenaline (0.5 microgram kg-1 min-1) for 14 days. 3. Propranolol pretreatment significantly enhanced the inotropic and chronotropic responses to isoprenaline. There were noticeable, but non-significant increases in inotropic sensitivity to noradrenaline and dopexamine, especially at higher dose levels. In the atenolol treatment group, there were significant increases in inotropic responses to dopexamine and isoprenaline and in depressor responses to isoprenaline. 4. Thus, chronic administration of propranolol increased responses mediated by both beta 1- and beta 2-adrenoceptors, whereas, atenolol selectively enhanced the inotropic responsiveness to dopexamine, which is mediated mainly by beta 2-adrenoceptors. 5. Isoprenaline pretreatment caused a significant decrease in inotropic sensitivity to dopexamine, isoprenaline and noradrenaline and a significant reduction in chronotropic responses to dopexamine. The tendency to reduced depressor responses to isoprenaline and dopexamine failed to reach significance. Pretreatment with noradrenaline decreased only the inotropic response to noradrenaline. 6. Thus, chronic isoprenaline treatment reduced the responsiveness of both beta 1- and beta 2-adrenoceptors, while chronic noradrenaline infusion only reduced beta 1-adrenoceptor-mediated responses. 7. There was no significant change in any of the dose-response curves to impromidine after any beta-adrenoceptor antagonist or agonist treatment. This indicates that there was no non-specific alteration in responsiveness and that the observed changes were likely to be associated with specific alterations in beta-adrenoceptor number or function.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/farmacología , Dopamina/análogos & derivados , Hemodinámica/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Perros , Dopamina/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Impromidina/administración & dosificación , Impromidina/farmacología , Isoproterenol/administración & dosificación , Isoproterenol/farmacología , Masculino , Contracción Miocárdica/efectos de los fármacos , Norepinefrina/administración & dosificación , Norepinefrina/farmacología , Propranolol/administración & dosificación , Propranolol/farmacología , Receptores Adrenérgicos beta 1/efectos de los fármacosRESUMEN
In order to explore the relationship between H2 R and the pathogenesis of asthma, we treated 19 stable asthmatic patients with H2-receptor agonist impromidine and observed its effect on bronchial hyperresponsiveness (BHR). The results showed that single dose inhalation of impromidine (2.5mg, in 13 cases) had no effect on the starting respiratory resistance (Rrs) and the minimum amount of cumulative dose (Dmin) to asthmatic airways, while repetitive inhalation of impromidine for 10 days (2. 5mg a day, in 6 cases) decreased the Rrs (P = 0.059) and increased the Dmin significantly (P < 0.05); and that H2R agonist impromidine could reduce the sensitivity of airway to methacholine and improve the BHR of asthmatic patients. The results suggest that H2R agonist may be used as anti-inflammatory drug to treat asthma and H2R may have protective role in the inflammatory reaction of asthmatic airways.
Asunto(s)
Asma/etiología , Agonistas de los Receptores Histamínicos/uso terapéutico , Impromidina/uso terapéutico , Receptores Histamínicos H2/fisiología , Adolescente , Adulto , Anciano , Resistencia de las Vías Respiratorias/efectos de los fármacos , Asma/tratamiento farmacológico , Hiperreactividad Bronquial/tratamiento farmacológico , Femenino , Agonistas de los Receptores Histamínicos/administración & dosificación , Humanos , Impromidina/administración & dosificación , Masculino , Persona de Mediana EdadRESUMEN
Cats were chronically implanted with electrodes for polygraphic recordings and cannulae for intracerebral microinjections in order to study the functional role of histaminergic innervation of the preoptic-anterior hypothalamus in sleep-wake control. alpha-Fluoromethylhistidine (alpha FMH, 50 micrograms in 1 microliter), a specific inhibitor of the histamine-synthesizing enzyme, when injected bilaterally into the preoptic area, where numerous histaminergic fibres and terminal-like structures are present, caused a significant increase in deep slow wave sleep (S2) and paradoxical sleep (PS) and a decrease in wakefulness. In contrast, microinjections of histamine (5 or 30 micrograms in 1 microliter) in the same area dose-relatedly increased wakefulness and decreased both slow wave sleep and paradoxical sleep. The effects of histamine were reduced by pretreatment with mepyramine (1 mg/kg i.p.), a well known histamine H1 receptor antagonist, and were mimicked by a local injection of impromidine (1 microgram in 1 microliter), a potent histamine H2 receptor agonist. Microinjections of mepyramine alone (120 micrograms in 1 microliter) caused an increase in slow wave sleep. These results suggest that preoptic histaminergic innervation is involved in sleep-wake control and that the action might be mediated via both H1 and H2 receptors.
Asunto(s)
Encéfalo/fisiología , Gatos/fisiología , Histamina/fisiología , Hipotálamo Anterior/fisiología , Área Preóptica/fisiología , Sueño/fisiología , Vigilia/fisiología , Animales , Relación Dosis-Respuesta a Droga , Electroencefalografía/efectos de los fármacos , Femenino , Histamina/administración & dosificación , Histamina/farmacología , Histidina Descarboxilasa/antagonistas & inhibidores , Hipotálamo Anterior/citología , Hipotálamo Anterior/efectos de los fármacos , Impromidina/administración & dosificación , Impromidina/farmacología , Masculino , Metilhistidinas/administración & dosificación , Metilhistidinas/farmacología , Microinyecciones , Área Preóptica/citología , Área Preóptica/efectos de los fármacos , Pirilamina/administración & dosificación , Pirilamina/farmacología , Sueño/efectos de los fármacos , Sueño REM/efectos de los fármacos , Sueño REM/fisiología , Factores de Tiempo , Vigilia/efectos de los fármacosRESUMEN
The aim of this study was to determine the role of histamine receptors in the nose. The effects of intranasal histamine challenge were compared with those of a specific H1-receptor agonist, betahistine and a specific H2-receptor agonist, impromidine, in 11 normal individuals and four with rhinitis. Sneezing, nasal irritation and hypersecretion were induced by histamine and the H1-receptor agonist, betahistine only. Nasal airway resistance (Rna) was measured by passive anterior rhinomanometry. Histamine, betahistine and impromidine all induced rises in Rna in both normal individuals and those with rhinitis but histamine had the most potent effect; the H2-receptor effect on Rna was predominant over that of the H1-receptor. The sensitivity to all three agonists was greater in the individuals with rhinitis.