Skvorak J P, Sutton E T, Rao P S, Dietz J R
Department of Physiology, College of Medicine, University of South Florida, Tampa 33612, USA.
Am J Physiol. 1996 Jul;271(1 Pt 2):R237-43. doi: 10.1152/ajpregu.1996.271.1.R237.
Our laboratory has recently shown that locally produced endothelin (ET) is involved in the atrial natriuretic peptide (ANP) response to a physical stimulus, stretch. The aim of this study was to determine if factors locally produced in the atria were involved in the ANP response to a chemical stimulus, anoxia. Reduced oxygen tension is a potent stimulus of ANP release, and our results show that, when isolated perfused atria were exposed to anoxic conditions, the ANP secretion rate increased by a maximum of 129 +/- 8% of the baseline. Exposure to anoxia caused neither an elevation in perfusate creatinine phosphokinase, a change in atrial morphology detectable by electron microscopy, nor interfered with the return toward the baseline ANP secretion rate with reoxygenation, suggesting that this response was not due to myocyte damage. When the atria were pretreated with either 3 microM BQ-123, an endothelin receptor inhibitor, or 10 microM indomethacin, a cyclooxygenase inhibitor, the ANP response to anoxia was nearly abolished. To clarify the association between ET and prostaglandins, we showed that the ANP response to 50 nM ET-1 was totally blocked at both high and low pressure by 10 microM indomethacin, but the increased contractility response to ET was unaffected. Therefore, we have concluded that the anoxia-induced ANP response is mediated by locally produced ET, which, in turn, stimulates the production of prostaglandins. Prostaglandins appear to be responsible for the increased ANP secretion rate.
我们实验室最近发现，局部产生的内皮素（ET）参与心房利钠肽（ANP）对物理刺激——牵张的反应。本研究的目的是确定心房局部产生的因子是否参与ANP对化学刺激——缺氧的反应。低氧张力是ANP释放的有效刺激，我们的结果表明，当分离的灌注心房暴露于缺氧条件下时，ANP分泌率最多增加至基线的129±8%。暴露于缺氧状态既未导致灌注液中肌酸磷酸激酶升高，也未引起电子显微镜可检测到的心房形态变化，且不影响复氧后ANP分泌率恢复至基线水平，这表明该反应并非由于心肌细胞损伤所致。当心房用3微摩尔BQ - 123（一种内皮素受体抑制剂）或10微摩尔吲哚美辛（一种环氧化酶抑制剂）预处理时，ANP对缺氧的反应几乎被消除。为了阐明ET与前列腺素之间的关联，我们发现，10微摩尔吲哚美辛在高压和低压下均完全阻断了ANP对50纳摩尔ET - 1的反应，但对ET增强的收缩反应无影响。因此，我们得出结论，缺氧诱导的ANP反应是由局部产生的ET介导的，而ET反过来又刺激前列腺素的产生。前列腺素似乎是ANP分泌率增加的原因。
