Corfield D R, Webber S E, Hanafi Z, Widdicombe J G
Department of Physiology, St George's Hospital Medical School, London.
Pulm Pharmacol. 1991;4(2):85-90. doi: 10.1016/0952-0600(91)90057-a.
The actions of bradykinin and the related compound lys-bradykinin have been studied on the tracheal circulation and tracheal smooth muscle of the sheep. Cranial tracheal arteries of ten anaesthetised and paralysed sheep were isolated and perfused at systemic arterial pressure; arterial inflow was measured with an electromagnetic flow probe. Tracheal smooth muscle tone was assessed by measuring the external diameter of the cranial trachea. Close arterial injection of bradykinin and lys-bradykinin (0.1 to 1000 pmoles) produced potent dose-dependent falls in tracheal vascular resistance: for bradykinin a maximum fall of -56.4% (52.3-60.5%, 95% confidence interval) and for lys-bradykinin -52.8% (46.5-59.1%). The ED50 values were 0.69 (0.51-1.32) and 1.46 (1.19-2.28) pmoles respectively. Small and inconsistent relaxation of tracheal smooth muscle was seen with the higher doses (greater than 1.9 pmoles) of both kinins. Intravenous indomethacin (5 mg.kg-1) increased the vasodilation produced by bradykinin and lys-bradykinin. Oxyhaemoglobin (4 microns at 0.35 ml.min-1) infused into the tracheal circulation almost abolished the responses to bradykinin and methacholine. The results indicate that in the sheep trachea bradykinin has little action on airway smooth muscle but is a potent dilator of the vasculature; bradykinin and lys-bradykinin are of similar potency suggesting the action may be via B2 receptors. While the vascular responses may be modulated by vasoconstrictor cyclo-oxygenase products the vasodilation is likely to be endothelium-dependent and not prostanoid-mediated.
已对缓激肽及相关化合物赖氨酰缓激肽在绵羊气管循环和气管平滑肌上的作用进行了研究。选取十只麻醉并麻痹的绵羊，分离其颅侧气管动脉，并在体动脉压下进行灌注；动脉流入量用电磁流量探头测量。通过测量颅侧气管的外径来评估气管平滑肌张力。向动脉内近距离注射缓激肽和赖氨酰缓激肽（0.1至1000皮摩尔）可使气管血管阻力产生显著的剂量依赖性下降：缓激肽最大下降-56.4%（52.3 - 60.5%，95%置信区间），赖氨酰缓激肽为-52.8%（46.5 - 59.1%）。半数有效剂量（ED50）值分别为0.69（0.51 - 1.32）和1.46（1.19 - 2.28）皮摩尔。两种激肽的较高剂量（大于1.9皮摩尔）可引起气管平滑肌轻微且不一致的舒张。静脉注射吲哚美辛（5毫克·千克⁻¹）可增强缓激肽和赖氨酰缓激肽产生的血管舒张作用。向气管循环中输注氧合血红蛋白（0.35毫升·分钟⁻¹时为4微米）几乎消除了对缓激肽和乙酰甲胆碱的反应。结果表明，在绵羊气管中，缓激肽对气道平滑肌作用很小，但却是血管的强效扩张剂；缓激肽和赖氨酰缓激肽效力相似，提示其作用可能通过B2受体介导。虽然血管反应可能受血管收缩性环氧化酶产物调节，但血管舒张可能依赖于内皮且非前列腺素介导。
