Central administration of
BHT 933, a highly selective alpha 2 agonist, to
pentobarbital-anesthetized, normotensive dogs resulted in a rapid, significant decrease in blood pressure. The maximal response occurred at 30 min and remained significantly decreased for 60 min. Concomitant with the hypotensive response was a decrease in heart rate. Pretreatment with
naloxone 15 min prior to the administration of
BHT 933 completely abolished the hypotensive response and significantly inhibited the
bradycardia. These results suggest a role for central opioidergic systems in the control of blood pressure which may serve as important sites of
antihypertensive drug action. The central regulation of sympathetic tone by catecholaminergic systems plays an important role in the control of cardiovascular function in both normal and pathological states. A high density of catecholaminergic nerve terminals is found in regions of the brainstem involved in cardiovascular control. Stimulation of the alpha receptors in these areas decreases peripheral sympathetic tone and subsequently lowers blood pressure. Recent histochemical evidence has demonstrated the presence of
opioid peptides in the nucleus tractus solitarii, nucleus ambiguous and hypothalamus as well as other discrete brain areas associated with cardiovascular control. Activation of the
opiate receptors in these brain areas decreases sympathetic tone and blood pressure. Additionally, both catecholaminergic and opioidergic systems have been implicated in the reaction to certain stimuli (i.e.,
pain, stress) which entail important hemodynamic adaptations. The similarity between the central
opiate and catecholaminergic systems suggests a relationship between the two systems in blood pressure control and a potential site of
antihypertensive drug action. The purpose of the present study was to determine if an opioidergic component is involved in the hypotensive action of
BHT 933 (
azepexole).
BHT 933 is a relatively new hypotensive agent which is a much more specific alpha 2 agonist than
clonidine.