ROLE OF VASCULAR ALPHA-1-ADRENOCEPTOR SUBTYPES IN THE PRESSOR-RESPONSE TO SYMPATHETIC-NERVE STIMULATION IN THE PITHED RAT

Previous studies suggest that systemic arterial pressure is tonically regulated by the interaction of peripheral sympathetic nerves with vas cular alpha-1A adrenoceptors in vivo. To explore this relationship fur ther, the present study examined the inhibitory effect of selective al pha-1A [5-methylurapidil (5-MU) and nifedipine (NIF)] and alpha-1B [ch loroethylclonidine (CEC)] antagonists on the presser response to elect rical stimulation (ES) of the spinal cord in pithed rats. Diastolic pr essure changes were measured in the presence of 5-MU or CEC and compar ed with control responses. Pretreatment with 5-MU (0.5 mg/kg i.v.) sig nificantly suppressed the ES presser response (50-80% inhibition) at a ll stimulation frequencies. Likewise, NIF (inhibitor of calcium influx associated with alpha-1A adrenoceptor activation) selectively inhibit ed the presser response to ES to the same degree as did 5-MU. CEC (25 mg/kg i.v.) also significantly shifted the ES response curve; however, this effect was mediated by activation of presynaptic alpha-2 recepto rs on sympathetic terminals because prior administration of idazoxan ( 5 mg/kg) prevented the inhibitory effect of CEC. Based on the potent i nhibitory effects of 5-MU and NIF on the ES presser response in the pi thed rat, it was concluded that vascular alpha-1A adrenoceptors reside in the synaptic region of neurovascular junction where they are prima rily activated by neuronal norepinephrine release. The inability of po stsynaptic alpha-1B adrenoceptor blockade (i.e., CEC administered to i dazoxan-treated rats) to antagonize the ES response and the poor inhib itory effect of NIF on the cirazoline (full alpha-1 agonist) dose-resp onse curve indicate that this adrenoceptor subtype may be located in p erisynaptic regions where they can be activated pharmacologically by e xogenous alpha-1 agonists or physiologically by plasma catecholamines.