title: Differential blocking effects of tetrodotoxin on double-peaked vasoconstrictor responses to periarterial nerve stimulation in canine isolated, perfused splenic artery.
abstract: 1. In the present study, we investigated the effects of progressive inhibition of neuronal sodium channels by increasing concentrations of tetrodotoxin (TTX; 1-30 nmol/L) on the double-peaked vasoconstrictor responses to electrical periarterial nerve stimulation in the canine isolated and perfused splenic artery. 2. Double-peaked vasoconstrictions (biphasic vasoconstrictor responses) were consistently observed in following electrical stimulation with 30 s trains of pulses at 1-10 Hz. At low frequencies of stimulation (1-3 Hz), a submaximal concentration of 3 nmol/L TTX had no effect on the first phase of the contractile response, but almost completely inhibited the second-phase response. At high frequencies (6-10 Hz), the two vasoconstrictor phases were almost equally inhibited by 50% by 3 nmol/L TTX. A three-fold increase in the concentration of TTX used (10 nmol/L) abolished the second-phase vasoconstriction at all stimulation frequencies tested, whereas this concentration of TTX failed to block the first-phase response. Further increasing the concentration of TTX to 30 nmol/L completely blocked the remaining first-phase response. 3. Treatment with 0.1 mumol/L prazosin did not modify the first-phase response to any of the stimulation frequencies in the presence of 3 nmol/L TTX. Moreover, 0.1 mumol/L prazosin had no affect on the second-phase response at low frequencies (1-3 Hz), while at high frequencies (6-10 Hz) it slightly, but significantly inhibited the second-phase response. The vasoconstrictor responses that persisted after 3 nmol/L TTX and 0.1 mumol/L prazosin were completely suppressed by subsequent application of 1 mumol/L alpha, beta-methylene ATP at all stimulation frequencies (1-10 Hz). 4. In conclusion, progressive inhibition of sodium channels by increasing the concentration of TTX may exert a more preferential inhibition on adrenergic rather than purinergic components, suggesting that TTX-sensitive sodium channels may have a more important role in determining the adrenergic rather than purinergic transmission of sympathetic nerves.
authors.affiliation: Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: X P
authors.initials: XP
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Chiba
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D026941:Sodium Channel Blockers; D013157:Splenic Artery / Q000187:drug effects* / Q000294:innervation* / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000317:Adrenergic alpha-Antagonists; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine; D011224:Prazosin