首页> 外文期刊>American Journal of Physiology >Ventilatory effects of gap junction blockade in the RTN in awake rats.
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Ventilatory effects of gap junction blockade in the RTN in awake rats.

机译:间隙连接阻滞对清醒大鼠RTN的通气作用。

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摘要

We tested the hypothesis that carbenoxolone, a pharmacological inhibitor of gap junctions, would reduce the ventilatory response to CO(2) when focally perfused within the retrotrapezoid nucleus (RTN). We tested this hypothesis by measuring minute ventilation (V(E)), tidal volume (V(T)), and respiratory frequency (F(R)) responses to increasing concentrations of inspired CO(2) (Fi(CO(2)) = 0-8%) in rats during wakefulness. We confirmed that the RTN was chemosensitive by perfusing the RTN unilaterally with either acetazolamide (AZ; 10 microM) or hypercapnic artificial cerebrospinal fluid equilibrated with 50% CO(2) (pH approximately 6.5). Focal perfusion of AZ or hypercapnic aCSF increased V(E), V(T), and F(R) during exposure to room air. Carbenoxolone (300 microM) focally perfused into the RTN decreased V(E) and V(T) in animals <11 wk of age, but V(E) and V(T) were increased in animals >12 wk of age. Glyzyrrhizic acid, a congener of carbenoxolone, did not change V(E), V(T), or F(R) when focally perfused into the RTN. Carbenoxolone binds to the mineralocorticoid receptor, but spironolactone (10 microM) did not block the disinhibition of V(E) or V(T) in older animals when combined with carbenoxolone. Thus the RTN is a CO(2) chemosensory site in all ages tested, but the function of gap junctions in the chemosensory process varies substantially among animals of different ages: gap junctions amplify the ventilatory response to CO(2) in younger animals, but appear to inhibit the ventilatory response to CO(2) in older animals.
机译:我们测试的假说羧苄索酮,缝隙连接的药理学抑制剂,当在梯形后核(RTN)内进行局部灌注时,会降低对CO(2)的通气反应。我们通过测量分钟通气量(V(E)),潮气量(V(T))和呼吸频率(F(R))对增加浓度的吸入CO(2)(Fi(CO(2) )在清醒过程中)= 0-8%)。我们证实,通过单侧灌注RTN与乙酰唑胺(AZ; 10 microM)或用50%CO(2)(pH约6.5)平衡的高碳酸血症人工脑脊液灌注RTN,可以实现化学敏感性。暴露于室内空气期间,AZ或高碳酸血症的aCSF的局部灌注会增加V(E),V(T)和F(R)。在小于11周龄的动物中,将羧苄酮(300 microM)局部灌注到RTN中会使V(E)和V(T)降低,但在大于12周龄的动物中V(E)和V(T)升高。甘草次酸是羧苄隆的同类物,当局部灌注到RTN中时不会改变V(E),V(T)或F(R)。 Carbenoxolone与盐皮质激素受体结合,但是螺碳内酯(10 microM)在与carbenoxolone结合使用时不会阻止年长动物体内V(E)或V(T)的抑制作用。因此,在所有测试的年龄中,RTN都是一个CO(2)化学感应位点,但是在不同年龄的动物之间,化学感应过程中缝隙连接的功能差异很大:缝隙连接会放大年轻动物对CO(2)的通气反应,似乎抑制了老年动物对CO(2)的通气反应。

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