Hemmung der metabolischen und zirkulatorischen (kardiovaskulären) Diazoxid-Wirkung durch alpha- und beta-Rezeptorenblockade

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Abstract
From the results reported it is evident that the effect of diazoxide is mediated by influencing the adrenergic system. The metabolic and circulatory effects of diazoxide are similar to those which can be observed under the influence of epinephrine: Decrease in serum immunoreactive insulin, increase in blood glucose and impaired glucose tolerance, increase in plasma free fatty acids, tachycardia, and widened pulse pressure. If one assumes that the well-known circulatory and metabolic effects of diazoxide are mediated by influencing the adrenergic system it can be exspected that these effects should change during alpha and beta receptor blockade. It was the purpose of the present study to evaluate the assumptions mentioned above. On three healthy persons and one patient suffering from an islet cell adenoma with hyperinsulinism blood glucose, plasma free fatty acids, serum immunoreactive insulin, heart rate, and blood pressure were measured before and during oral administration of diazoxide. The results obtained as a control series in fasting state and under the influence of an intravenous glucose load were compared with the effects of intravenous phentolamine infusion and oral administration of propranolol respectively under otherwise the same conditions. In all cases the diazoxide induced inhibition of insulin secretion and the impaired glucose tolerance could be reversed by phentolamine. The effects of diazoxide on plasma free fatty acids and on heart rate and blood pressure, however, were only inhibited by beta receptor blockade with propranolol. Bei klinischen Studien konnten unter Diazoxidgaben metabolische und zirkulatorische Wirkungen beobachtet werden, wie sie weitgehend durch adrenerge Substanzen auslösbar sind. Dazu gehören Abfall des Seruminsulins, verminderte Glucosetoleranz, Anstieg der freien Fettsäuren und Tachykardie. Die metabolischen und zirkulatorischen Veränderungen durch Diazoxid konnten bei den klinischen Untersuchungen durch Gaben von alpha- und beta-Rezeptorenblockern weitgehend aufgehoben werden. Diese Untersuchungsergebnisse weisen darauf hin, daß der Wirkungsmechanismus von Diazoxid in einer Beeinflussung des adrenergen Systems liegt.

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