Haxhiu M A, Haxhiu-Poskurica B, Moracic V, Carlo W A, Martin R J
Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
Respir Physiol. 1990 Dec;82(3):267-77. doi: 10.1016/0034-5687(90)90097-i.
In adult animals, airway fluid secretion is enhanced reflexly via central nervous system pathways, and locally by mediators such as substance P. To evaluate the role of maturation on these regulatory mechanisms, we compared the effects of reflex stimulation and intravenous substance P administration on airway secretion in anesthetized, paralyzed and artificially ventilated piglets, 9 to 22 days of age, and older piglets all aged 10 weeks. Airway secretion was monitored by counting the hillocks appearing in the upper trachea in an exposed field of tracheal epithelium (1.2 cm2) coated with powdered tantalum. In younger animals, mechanical stimulation of the larynx had no discernible effect on tracheal submucosal gland secretion. Neither excitation of airway irritant receptors nor stimulation of pulmonary C-fiber receptors by capsaicin caused a significant increase of fluid secretion from tracheal submucosal glands. In addition, stimulation of peripheral chemoreceptors by ventilating animals with 12% O2 in N2, and 6% O2 in N2, failed to induce a substantial change in airway secretion, when compared with number of hillocks in the control period. Furthermore, administration of sodium cyanide had little or no effect on baseline secretion. In contrast, to the weak reflex responses in younger piglets electrical stimulation of the vagus nerve caused the number of hillocks to increase on average by 16.3 +/- 2.3 (P less than 0.01). In addition, local application of a pledget soaked in solution of methacholine caused the number of hillocks to increase by 32.1 +/- 5.2 (P less than 0.01). Intravenous administration of substance P also induced an augmentation in fluid secretion. Increase in concentration of substance P (10(-8), 10(-7), 10(-6), and 10(-5) M, 1 ml) was associated with a concomitant elevation in the number of activated submucosal glands (5.3 +/- 2.6, 10.0 +/- 4.4, 27.1 +/- 4.5, 41 +/- 5). In older piglets, stimulation of laryngeal mucosa, airway irritant receptors, as well as stimulation of pulmonary C-fiber receptors induced a significant increase in tracheal secretion, although stimulation of peripheral chemoreceptors had no effect on airway secretion. These data suggest that reflex responses of submucosal glands are weak during early postnatal development, however, tracheal submucosal glands do respond to exogenously administered cholinergic substances and tachykinin peptides.
在成年动物中，气道液体分泌可通过中枢神经系统途径反射性增强，也可通过诸如P物质等介质局部增强。为了评估成熟对这些调节机制的作用，我们比较了反射刺激和静脉注射P物质对9至22日龄麻醉、麻痹并人工通气的仔猪以及所有10周龄的较大仔猪气道分泌的影响。通过计数涂有粉状钽的气管上皮暴露区域（1.2平方厘米）中气管上部出现的小丘来监测气道分泌。在较年幼的动物中，对喉部的机械刺激对气管黏膜下腺分泌没有明显影响。气道刺激性受体的兴奋或辣椒素对肺C纤维受体的刺激均未导致气管黏膜下腺液体分泌显著增加。此外，与对照期的小丘数量相比，用含12%氧气的氮气和含6%氧气的氮气对动物进行通气刺激外周化学感受器，未能引起气道分泌的实质性变化。此外，给予氰化钠对基础分泌几乎没有影响。相比之下，年幼仔猪的反射反应较弱，迷走神经电刺激使小丘数量平均增加16.3±2.3（P<0.01）。此外，局部应用浸泡在乙酰甲胆碱溶液中的棉球使小丘数量增加32.1±5.2（P<0.01）。静脉注射P物质也可诱导液体分泌增加。P物质浓度增加（10⁻⁸、10⁻⁷、10⁻⁶和10⁻⁵M，1毫升）与激活的黏膜下腺数量相应增加有关（5.3±2.6、10.0±4.4、27.1±4.5、41±5）。在较大的仔猪中，刺激喉黏膜、气道刺激性受体以及刺激肺C纤维受体均导致气管分泌显著增加，尽管刺激外周化学感受器对气道分泌没有影响。这些数据表明，出生后早期黏膜下腺的反射反应较弱，然而，气管黏膜下腺确实对外源性给予的胆碱能物质和速激肽肽有反应。
