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 vascular alpha-1A adrenoceptors in vivo. To explore this relationship further, the present study examined the inhibitory effect of selective alpha-1A [5-methylurapidil (5-MU) and nifedipine (NIF)] and alpha-1B [chloroethylclonidine (CEC)] antagonists on the pressor response to electrical stimulation (ES) of the spinal cord in pithed rats. Diastolic pressure changes were measured in the presence of 5-MU or CEC and compared with control responses. Pretreatment with 5-MU (0.5 mg/kg i.v.) significantly suppressed the ES pressor response (50-80% inhibition) at all stimulation frequencies. Likewise, NIF (inhibitor of calcium influx associated with alpha-1A adrenoceptor activation) selectively inhibited the pressor 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 receptors on sympathetic terminals because prior administration of idazoxan (5 mg/kg) prevented the inhibitory effect of CEC. Based on the potent inhibitory effects of 5-MU and NIF on the ES pressor response in the pithed rat, it was concluded that vascular alpha-1A adrenoceptors reside in the synaptic region of neurovascular junction where they are primarily activated by neuronal norepinephrine release.(ABSTRACT TRUNCATED AT 250 WORDS)
Hoechst-Roussel Pharmaceuticals, Inc., Neuroscience Business Unit, Somerville, New Jersey.
H M
HM
Vargas
L
L
Zhou
A J
AJ
Gorman
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000294:innervation*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003655:Decerebrate State; D004146:Dioxanes / Q000494:pharmacology; D004558:Electric Stimulation; D019329:Idazoxan; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*
D004146:Dioxanes; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; C057446:5-methylurapidil; C051731:chlorethylclonidine; D009543:Nifedipine; D003000:Clonidine; D019329:Idazoxan