Herman C A, Robleto D O, Reitmeyer S T, Martinez L A, Herman R P
Department of Biology, New Mexico State University, Las Cruces 88003.
Biomed Biochim Acta. 1988;47(10-11):S178-81.
While the cardiovascular effects of the sulfidopeptide leukotrienes (LTs) have been well studied in mammals, their effects are not well known in lower vertebrates. American bullfrogs (Rana catesbeiana) were cannulated in the right sciatic artery and left sciatic vein. In some studies an additional ventricular cannula was implanted. LTC4, LTD4, and LTE4 were compared for their cardiovascular actions by infusion via the sciatic vein into the unanesthetized animals. While all three leukotrienes decreased mean arterial pressure (MAP) and increased heart rate (HR), LTC4 was found to be more potent than the other leukotrienes. In bullfrogs with ventricular cannulae to measure ventricular pressure (VP) and its derivative (+ dP/dt), LTC4 had negative inotropic effects which were blunted by indomethacin (4 mg/kg-bw). 3H-LTC4 metabolism studies were carried out using blood and plasma to examine conversion to other products. Following incubation for 12 min and extraction by C18 Sep-Pak cartridges, samples were analyzed by high performance liquid chromatography. In whole blood, but not in plasma, 3H-LTC4 was rapidly converted to a compound with the retention time of the LTD4 standard. Little conversion to LTE4 was observed within the time course of the experiment. The data suggest that cardiovascular effects of LTC4 may be greater than those observed, since LTC4 is rapidly metabolized to a less active compound. The effects of LTC4 may, in part, be due to stimulation of synthesis of cyclooxygenase metabolites. The ability to record the effects of leukotrienes uncomplicated by effects on coronary arteries make the bullfrog an excellent model for comparative studies on the cardiovascular effects of leukotrienes.
虽然硫肽白三烯（LTs）对哺乳动物心血管系统的影响已得到充分研究，但其对低等脊椎动物的影响尚不明确。对美国牛蛙（牛蛙）进行右坐骨动脉和左坐骨静脉插管。在一些研究中，还植入了额外的心室插管。通过坐骨静脉向未麻醉的动物输注LTC4、LTD4和LTE4，比较它们的心血管作用。虽然所有三种白三烯均降低平均动脉压（MAP）并增加心率（HR），但发现LTC4比其他白三烯更有效。在植入心室插管以测量心室压力（VP）及其变化率（+dP/dt）的牛蛙中，LTC4具有负性肌力作用，吲哚美辛（4mg/kg体重）可减弱这种作用。使用血液和血浆进行3H-LTC4代谢研究，以检查其向其他产物的转化。孵育12分钟后，用C18 Sep-Pak柱提取样品，然后通过高效液相色谱进行分析。在全血中，而非血浆中，3H-LTC4迅速转化为一种保留时间与LTD4标准品相同的化合物。在实验过程中，几乎未观察到向LTE4的转化。数据表明，LTC4的心血管作用可能比观察到的更大，因为LTC4会迅速代谢为活性较低的化合物。LTC4的作用可能部分归因于对环氧合酶代谢产物合成的刺激。记录白三烯的作用而不受冠状动脉影响的能力，使牛蛙成为研究白三烯心血管作用的理想比较模型。
