Effects of hydralazine on cardiac responsiveness to adrenergic agonists in streptozotocin-induced diabetic rats.

The present investigation was undertaken to study the effects of hydralazine treatment (50 mg/kg/day, p.o.) on methoxamine and isoproterenol-induced responses in cardiac preparations of control and streptozotocin (STZ)-induced diabetic rats. Triiodothyronine (T3) and thyroxine (T4) levels were found to be significantly decreased in diabetic rats and this decrease was prevented by hydralazine treatment. Methoxamine and isoproterenol produced a dose-dependent positive chronotropic and positive inotropic effect in right and left atrium respectively. These responses to methoxamine were significantly increased, whereas, those to isoproterenol were significantly decreased in preparations obtained from diabetic rats. Hydralazine treatment did not alter the isoproterenol-induced chronotropic effect in right atrium. However, it prevented the diabetes-induced increase in responsiveness to methoxamine in this preparation. Hydralazine increased significantly the inotropic response to methoxamine and isoproterenol in left atrium of control and diabetic rats. Both the pD2 value and maximum response were increased. The studies indicates that hydralazine-induced alterations in the responsiveness to methoxamine could partly be due to its ability to prevent diabetes-induced hypothyroidism. The effects of hydralazine on isoproterenol-induced responses appear to be independent of hypothyroidism, and some post-receptor mechanisms and metabolic derangements might be responsible for this effect.

Aspecto histológico das arteríolas intramiocárdicas, nas situaçöes da vasodilataçäo e vasoconstricçäo induzida por drogas / Histologic aspects of intramyocardial arterioles, during vasodilation and vasoconstriction induced by drugs

O aspecto histol[ogico das arteríolas intramiocárdicas do cäo, foi estudado em diferentes condiçöes hemodinâmicas, induzidas por drogas. A avaliaçäo das condiçöes hemodinâmicas foi feita pela medida das pressöes de átrio direito e aorta e pelo fluxo sangüíneo coronário obtido por fluxômetro eletromagnético. A avaliaçäo da motricidade arteriolar foi feita pela medida da relaçäo parede/luz dos vasos intramiocárdicos, em cortes histológicos corados pela HE. Os resultados revelaram uma relaçäo parede/luz de 1:1 para os casos controle, 0,3 para as situaçöes de vasodilataçäo e 1,5 para as condiçöes de vasoconstricçäo. Os autores sugerem que a expressäo histológica das arteríolas intramiocaárdicas, em condiçöes de vasodilataçäo e vasoconstricçäo, pode representar os limites da expressäo hemodinâmica da curva de autoregulaçäo circulatória coronariana

Contractile reactivity of the perfused mesenteric vascular bed from sinoaortic denervated rats to norepinephrine, methoxamine and verapamil

The contractile reactivity to noropinephrine, methoxamine, and verapamil of the perfused mesenteric vascular bed from sinoaortic denervated (SAD) and sham-operated (SO) rats was studied 3 to 30 days after surgery. A gradual but incomplete reduction of arterial hypertension was observed in SAD rats throughout the study. The norepinephrine-and methoxamine-induced dose-response curves were similar in both SAD and SO groups on day 3, but shifted to the left on days 7 and 15 and demonstrated a tendency to shift to the right at 30 days. Verapamil-induced vasodilation was similar in both groups. Enhanced mesenteric vascular responsiveness to endogenous catecholamines could contribute to the increased vascular resistance

Efeito inibidor de aminas simpatomiméticas nas respostas contráteis do duodeno de rato ao cálcio e ao bário / The inhibitory effect of sympathomimetics amines in the contractle responses of rat duodenum to calcium and barium

O duodeno de rato imerso em uma soluçäo de Tyrode sem cálcio responde com contraçöes equivalentes ao bário e ao cálcio. As respostas contráteis ao cálcio säo quantitativamente bloqueadas tanto por alfa como por beta simpatomiméticos. A açäo inibidora dos simpatomiméticos é reduzida pelos agentes simpatolíticos correspondentes e também pela efedrina, que näo possui atividade intrínseca. A açäo dos simpatomiméticos foi acentuadamente reduzida pela despolarizaçäo do duodeno com excesso de potássio. Os simpatolíticos fentolamina e propranolol têm efeito semelhante ao dos anestésicos locais, isto é, inibiçäo das contraçöes produzidas por bário tanto em soluçäo de Tyrode normal como com excesso de potássio; eles näo interferem com as respostas ao cálcio em condiçöes normais. Conclui-se que a despolarizaçäo do duodeno de rato rompe a interaçäo normal dos simpatomiméticos com os receptores adrenérgicos; a açäo das drogas na preparaçäo despolarizada é por uma interferência inespecífica à permeabilidade dos íons na membrana celular

Vascular desensitisation--possible role of prostaglandins.

Prolonged exposure to noradrenaline (NA) brings about an increase in the release of prostaglandin (PG)-like material from rat aortic strip. The release is greater with oxymetazoline while methoxamine decreases it. These effects are blocked by yohimbine and prazosin respectively. Pretreatment with 6-OHDA or reserpine diminishes the release of PG-like material. Barium chloride, a non-specific spasmogen, does not affect the release significantly. It appears therefore that the source of PG-like material is presynaptic and that its release mechanism is linked to an alpha 2 (alpha 2) adrenoceptor. It is proposed that this release of PG-like material contributes to the development of desensitisation in vascular tissue.

Diferentes efectos de la adrenalina sobre el músculo liso traqueal de Erythrocebus patas: predominio de los receptores adrenérgicos alfa / Diferent effects of adrenaline on the Erythrocebus patas tracheal smooth muscle: predominance of alpha-adrenergic receptors

Al comparar la reacción del músculo liso traqueal del cobayo a la adrenalina con la obtenida en la tráquea aislada del mono Erythrocebus patas (E. patas), se encontró que en este último la catecolamina producía contracciones repetidas de duración breve en lugar de la relajación ordinaria que induce en la tráquea del cobayo y de otras especies, incluyendo al hombre. En vista de esto se decidió estudiar el efecto de un agonista (metoxamina) y de un antagonista (zolertina) selectivos para los receptores adrenérgicos alfa sobre la cadena traqueal en ambas especies. La administración de metoxamina al baño de tejido aislado produjo contracción de las tráqueas de ambas especies relacionada con la concentración del agonista. Swin embargo, el músculo liso de Erythrocebus patas resultó ser claramente más sensible que el del cobayo al efecto contráctil de la metoxamina. El contacto previo de las preparaciones con zolertina produjo disminución en la magnitud de las reacciones a la metoxamina. Aunque este fenómeno se observó en las tráqueas de las dos especies, el desplazamiento de las curvas de dosis y respuesta de la metoxamina hacia la derecha ocurrió en el tejido del primate a concentraciones diez veces menores que en el caso del cobayo. Estos resultados sugieren que en el músculo liso traqueal de Erythrocebus patas existe un predominio de los receptores adrenérgicos alfa, lo cual si bien difiere del tejido humano normal parecería tener semejanza con lo que ocurre en el músculo liso traqueobronquial del paciente asmático