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首页> 外文期刊>Clinical and experimental pharmacology & physiology >Differential blocking effects of tetrodotoxin on double-peaked vasoconstrictor responses to periarterial nerve stimulation in canine isolated, perfused splenic artery.
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Differential blocking effects of tetrodotoxin on double-peaked vasoconstrictor responses to periarterial nerve stimulation in canine isolated, perfused splenic artery.

机译:河豚毒素对犬离体灌注脾动脉中对动脉周围神经刺激的双峰血管收缩反应的差异阻断作用。

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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.
机译:1.在本研究中,我们研究了通过增加河豚毒素(TTX; 1-30 nmol / L)的浓度逐步抑制神经元钠通道对离体和分离出的犬对电动脉周围神经刺激的双峰血管收缩反应的影响。灌注脾动脉。 2.在以1-10 Hz的30 s脉冲序列进行电刺激后,始终观察到双峰血管收缩(双相血管收缩反应)。在低频刺激下(1-3 Hz),亚最大浓度的3 nmol / L TTX对第一阶段的收缩反应没有影响,但几乎完全抑制了第二阶段的反应。在高频率(6-10 Hz)下,3 nmol / L TTX几乎相等地抑制了两个血管收缩相50%。在所有测试的刺激频率下,使用的TTX浓度增加了三倍(10 nmol / L)消除了第二阶段的血管收缩,而该TTX的浓度未能阻止第一阶段的反应。将TTX的浓度进一步增加至30 nmol / L完全阻断了剩余的第一相响应。 3.在存在3 nmol / L TTX的情况下,用0.1μmol/ L的哌唑嗪进行处理不会改变对任何刺激频率的第一阶段响应。此外,0.1μmol/ L的哌唑嗪在低频(1-3 Hz)下对第二相响应没有影响,而在高频(6-10 Hz)下对第二相响应没有影响,但显着抑制了第二相响应。随后在所有刺激频率(1-10 Hz)下施加1μmol/ Lα,β-亚甲基ATP可以完全抑制3 nmol / L TTX和0.1μmol/ L哌唑嗪后持续存在的血管收缩反应。 4.总之,通过增加TTX的浓度来逐步抑制钠通道可能对肾上腺素而非嘌呤能成分产生更优先的抑制作用,这表明TTX敏感的钠通道可能在确定肾上腺素而非嘌呤能传递中起更重要的作用。交感神经。

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