DO CENTRALLY-ACTING ANTIHYPERTENSIVE DRUGS ACT AT NONADRENERGIC AS WELL AS ALPHA-2 ADRENOCEPTOR SITES

Rabbits were treated with guanabenz, clonidine and rilmenidine for 6 days via osmotic minipumps. Blood pressure, heart rate and responses to intracisternal clonidine were measured after 1 and 6 days treatment. Radioligand binding to forebrain and hindbrain membranes after 6 days treatment was examined using [H-3]yohimbine to measure the number of adrenergic binding sites and [H-3]clonidine and [H-3]idazoxan to assess nonadrenergic imidazoline sites. No change in nonadrenergic imidazoline binding was observed but adrenergic binding was decreased in forebrain and hindbrain by guanabenz and in hindbrain by clonidine treatment. Resting heart rate was decreased after 1 day's treatment with partial recovery by day 6. At this time heart rate was significantly reduced in the clonidine and rilmenidine treated groups but not the guanabenz group. No significant change in baseline blood pressure was observed in normotensive rabbits. Both depressor and bradycardia responses to intracisternal clonidine were attenuated after 1 day's dosing but only depressor responses were influenced after 6 days. Blood pressure and heart rate thus appeared to be regulated independently. It is possible that imidazoline receptors Predominate in the central control of blood pressure while central alpha-2 adrenoceptors play a greater part in heart rate regulation.