Investigation into mechanism of lack of reflex tachycardia in response to hypotensive action of indoramin in dogs

Abstract

In animals and man, the selective alpha 1-adrenoceptor antagonist indoramin reduces arterial pressure without increasing heart rate. We studied this mechanism of absence of reflex tachycardia in anaesthetised dogs. Indoramin reduced (p less than 0.05) arterial pressure with no reflex increase in heart rate, whereas phenoxybenzamine reduced (p less than 0.05) pressure but increased (p less than 0.05) heart rate. Atropine and propranolol pretreatment, vagotomy and division of the cardio-accelerator nerve did not prevent the reduction (p less than 0.05) in arterial pressure and heart rate seen with indoramin. Mexiletine, a drug which has membrane-stabilising activity, had no effect on heart rate or arterial pressure. Mexiletine and indoramin did not affect the increases in heart rate produced by stimulation of the cardio-accelerator nerve. Indoramin reduced (p less than 0.05) the increases in heart rate and arterial pressure produced by bilateral carotid occlusion, and potentiated the arterial pressure reduction but attenuated the heart rate response to intravenous isoprenaline. It also reduced (nonsignificantly) the responses to intravenous noradrenaline and phenylethylamine but had no effect on the arterial pressure and heart rate responses to bilateral central vagal stimulation. We conclude that the absence of the reflex tachycardia with hypotensive doses of indoramin does not result from the myocardial membrane-stabilising action of indoramin or from alteration in sympathetic and parasympathetic activity, but may occur partly from a reduction in baroreceptor sensitivity.