Cardioregulatory properties of indoramin in the rat

The antihypertensive action of the competitive alpha-adrenoceptor antagonist indoramin is not accompanied by reflex tachycardia in animals or man. The possibility that the established local anaesthetic property of indoramin is involved in its cardioinhibitory action has been investigated. Indoramin evoked a dose-dependent bradycardia in anaesthetized/pithed rats. The decrease in heart rate was slightly greater than that evoked in anaesthetized intact animals suggesting that indoramin had a direct action on the heart. Reflex tachycardia was simulated in pithed rats be increasing the frequency of cardiac nerve stimulation from 0.3 to 1 Hz. Indoramin and the local anaesthetic agents, lignocaine and procaine, reduced the positive chronotropic response without markedly altering the basal rate. The response curves were parallel. In contrast, phentolamine decreased the positive chronotropic response, but only at high doses which were associated with a marked decrease in the basal rate. Thymoxamine and prazosin had so significant effects on the chronotropic response. These experiments suggest that the cardioregulatory action of indoramin is attributable to its local anaesthetic property had this action further distinguishes it from the other alpha-adrenoceptor antagonists tested.