1 The cardioregulatory properties of the a1-adrenoceptor blocker indoramin have been compared with those of prazosin in the anaesthetized rat. The effects of autonomic blockade on heart rate responses evoked by these two agents and their effects on blood pressure and heart rate after peripheral or central administration have been compared. 2 Cumulative administration of indoramin (0.8-25.6 mg kg-' i.v.) evoked significant decreases in arterial blood pressure and a concomitant bradycardia. Pithing or autonomic blockade, by pretreatment with a combination of practolol and bilateral vagotomy, prevented the bradycardia evoked by indoramin (0.8-3.2 mg kg-' i.v.). Atropine sulphate pretreatment abolished the bradycardia until a cumulative dose of 25.6 mg kg-' (i.v.) of indoramin had been reached. Bilateral vagotomy, intravenous administration of atropine methylnitrate or practolol pretreatment attenuated the bradycardia. 3 Prazosin (0.02-0.64mg kg-i.v.) evoked a fall in arterial blood pressure of similar magnitude to that observed following indoramin. A bradycardia was evoked only at a relatively high dose (0.64mg kg-' i.v.). 4 Intracisternal injection of indoramin or prazosin evoked bradycardia and hypotension at a dose which had no effect after intravenous injection (25 Jpg). Intracerebroventricular injection ofindoramin (25 gtg) had no significant effect on heart rate or blood pressure compared to control values, whereas prazosin (25 jig) evoked a significant tachycardia and hypotension.5 It is concluded that the bradycardia evoked by indoramin in the rat is not due to a direct action on the heart except possibly at high doses. Central c~,-adrenoceptor blockade, possibly in the brainstem region, results in a bradycardia and this may explain the lack of reflex tachycardia following the administration of indoramin.
In patas monkeys fed a high cholesterol diet, chronic dosing with the antihypertensive agent indoramin increases the cholesterol ratio by raising the plasma HDL-C concentration. Epidemiological evidence suggests that increasing HDL-C reduces the incidence of coronary heart disease (CHD). If, therefore, indoramin is able to evoke these changes in man it may be expected to favourably influence the progress of CHD.
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