Cutaneous arterial and venous alpha receptor blocking activity following intraduodenal indoramin to dogs

Indoramin is a selective α 1 receptor antagonist, with pharmacologic activity similar to prazosin. However, indoramin differs from prazosin in that indoramin has membrane stabilizing activity; does not cause reflex tachycardia, first dose syncope, or orthostatic hypotension; and requires several days for onset of its antihypertensive action. Thus, indoramin may lower blood pressure independent of arterial or venous α 1 adrenoceptor blockade. This study compares the relative arterial and venous α 1 adrenoceptor blocking activity of indoramin and prazosin, following intraduodenal (id) administration, in the canine hindpaw preparation perfused at constant flow, to their blood pressure lowering activity. Indoramin (5 and 20 mg/kg, id) inhibited the arterial and venous pressor responses to sympathetic nerve stimulation (SNS) and norepinephrine (NE). No significant differences in the magnitude of arterial and venous blockade existed. Blockade of α 1 adrenoceptors was maximal at 5 mg/kg of indormin. In contrast, 20 mg/kg of indoramin lowered mean arterial blood pressure (MAP) but did not affect paw perfusion pressure (PP). Prazosin (0.25 and 1.0 mg/kg, id) produced both dose‐related α 1 adrenoceptor blockade and reduction of MAP. Prazosin was more effective as an inhibitor of venous vs. arterial responses to SNS, and produced a different profile of inhibition of SNS than indoramin. Thus, indoramin differs from prazosin as an inhibitor of α 1 adrenoceptors of the canine paw. Since indoramin does not lower MAP in doses which block α 1 adrenoceptors of the paw and does not lower PP in the decentralized paw in doses which lower MAP, we conclude that indoramin acutely lowers MAP in the dog by a mechanism unrelated to postsynaptic α 1 receptor blockade, and may inhibit a subtype of α 1 adrenoceptor different from that inhibited by prazosin.