Potential of alpha blockade in treating human hypertension: a role for indoramin

Alpha-adrenergic activity mediated by the autonomic nervous system, consisting of the release of norepinephrine and its engagement by the alpha receptors, is a recognized pathway for arteriolar vasoconstriction. The pathway is well traveled in acute reactions to emotion and stress, but this complicity in chronic hypertension other than pheochromocytoma has been more difficult to show. Among the reasons for the difficulty is the failure to develop an animal model of hypertension mediated through the nervous system. Another reason is the uncertainty as to whether or not measurements of plasma norepinephrine really reflect what is happening at the synapse. Nevertheless, treating essential hypertension with alpha blockade has always been attractive to investigators. The potential has remained tantalizing by the occasional clinical success, at least in depressor terms, of the early ganglionic blocking agents. However, until quite recently that potential has been held out of reach by the unpredictability of these drugs, the undiscriminating nature of their gross blockade of the autonomic nervous system, and their baggage of disturbing side effects. Now it can be reported that a succession of alpha-adrenergic blocking agents, with increasing presynaptic specificity, has assembled indirect but persuasive evidence of alpha-adrenergic participation in definable forms of hypertension. They include guanethidine, phentolamine, phenoxybenzamine, prazosin, and now indoramin. In mapping autonomic pressor activity as indicated by the response to blockade, these pharmacologic probes have made abundantly clear a central fact that we always knew but tended sometimes to forget: namely, that hypertension is a heterogeneous phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)