DESENSITIZATION AND DOWN-REGULATION OF BRAIN ALPHA-2-ADRENOCEPTORS BY CENTRALLY ACTING ANTIHYPERTENSIVE DRUGS

Rabbits were treated with intravenous clonidine (8 mumol kg‐1 day‐1), guanabenz (20 mumol kg‐1 day‐1), rilmenidine (80 mumol kg‐1 day‐1) or vehicle via osmotic minipumps. After 6 days treatment mean arterial pressure (MAP), pressor responses to intravenous alpha‐methyl noradrenaline and depressor responses to intracisternal clonidine were studied, and [3H]‐yohimbine binding to forebrain and hindbrain examined in vitro. Clonidine, guanabenz and rilmenidine had similar effects on MAP and caused a similar attenuation of the depressor response to intracisternal clonidine, but only guanabenz attenuated pressor responses to intravenous alpha‐methyl noradrenaline. Rilmenidine had no effect on [3H]‐yohimbine binding to brain membranes. Clonidine treatment decreased binding in hindbrain while guanabenz treatment decreased binding in both fore‐ and hindbrain. Thus, the depressor effects of chronic treatment did not correlate with the effects on [3H]‐ yohimbine binding sites in rabbit brain suggesting that the blood pressure lowering effects of many centrally acting antihypertensive drugs are not necessarily dependent on binding to the alpha 2‐ adrenoceptor site labelled by [3H]‐yohimbine. 1990 The British Pharmacological Society