Hm. Vargas et al., ROLE OF VASCULAR ALPHA-1-ADRENOCEPTOR SUBTYPES IN THE PRESSOR-RESPONSE TO SYMPATHETIC-NERVE STIMULATION IN THE PITHED RAT, The Journal of pharmacology and experimental therapeutics, 271(2), 1994, pp. 748-754
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.