Orr J A, Ernst M, Carrithers J, Shirer H W
Department of Physiology and Cell Biology, University of Kansas, Lawrence 66045.
Respir Physiol. 1990 May-Jun;80(2-3):203-17. doi: 10.1016/0034-5687(90)90084-c.
Intravenous infusion of HCl has been shown to elicit the release of thromboxane A2 (TxA2) which alters blood pressure and breathing independent of reductions in circulating blood pH. The present experiments were designed to determine if the release of serotonin (5-HT) in the anesthetized cat contributed to cardiorespiratory responses during acid infusion and, furthermore to define the source of TxA2, viz. blood or other tissues. To infuse HCl into the bloodstream without reducing circulating blood pH (= neutral acid-base infusion), an extracorporeal arteriovenous shunt (20 ml/min) between the femoral artery and femoral vein was installed. Into this loop, acid (0.25 M HCl), and approximately 10 cm downstream, base (0.25 M NaOH) could be infused whereby blood pH could be locally reduced in the blood within the loop. This procedure was performed in three groups of cats: one group which received no drugs, a second group that was pretreated with indomethacin (2.5 mg/kg) and a third group that received the 5-HT2 receptor antagonist, ketanserin (0.75 mg/kg), prior to the infusion. During neutral acid-base infusion in the nontreated animals, right ventricular blood pressure (PRV) increased and systemic arterial blood pressure (Pa) decreased. Respiratory frequency was increased, but total ventilation was not elevated because of a concomitant fall in tidal volume (VT). The response was transient and could not be evoked with repetitive infusions of HCl and NaOH. These responses were significantly attenuated in the indomethacin-treated animals, but persisted in the cats pretreated with ketanserin. In addition, TxB2, the stable degradation metabolite of TxA2, was elevated during the acid/base infusion, but there were no measurable changes in plasma 5-HT concentration. The source of TxA2 was likely to be the blood since TxB2 was increased in plasma when acid and base were added to blood in vitro. We conclude from these experiments that transient cardiorespiratory responses to HCl infusion are mediated by the release of TxA2 from the blood and do not involve serotonin.
静脉输注盐酸已被证明可引发血栓素A2（TxA2）的释放，这会改变血压和呼吸，且与循环血液pH值的降低无关。本实验旨在确定麻醉猫体内血清素（5-HT）的释放是否在酸输注期间对心肺反应有影响，此外还旨在确定TxA2的来源，即血液或其他组织。为了在不降低循环血液pH值的情况下将盐酸输注到血液中（即中性酸碱输注），在股动脉和股静脉之间安装了体外动静脉分流装置（20毫升/分钟）。在这个回路中，可以输注酸（0.25M盐酸），并且在大约下游10厘米处可以输注碱（0.25M氢氧化钠），从而使回路内血液的pH值局部降低。该操作在三组猫中进行：一组未接受药物治疗，第二组在输注前用吲哚美辛（2.5毫克/千克）预处理，第三组在输注前接受5-HT2受体拮抗剂酮色林（0.75毫克/千克）。在未治疗动物的中性酸碱输注期间，右心室血压（PRV）升高，全身动脉血压（Pa）降低。呼吸频率增加，但由于潮气量（VT）同时下降，总通气量并未升高。该反应是短暂的，重复输注盐酸和氢氧化钠无法诱发。这些反应在吲哚美辛治疗的动物中显著减弱，但在酮色林预处理的猫中持续存在。此外，TxA2的稳定降解产物TxB2在酸碱输注期间升高，但血浆5-HT浓度没有可测量的变化。TxA2的来源可能是血液，因为在体外向血液中添加酸和碱时，血浆中的TxB2会增加。我们从这些实验中得出结论，对盐酸输注的短暂心肺反应是由血液中TxA2的释放介导的，不涉及血清素。
