Cyclic ADP-ribose is the primary trigger for hypoxic pulmonary vasoconstriction in the rat lung in situ
Cyclic ADP-ribose is the primary trigger for hypoxic pulmonary vasoconstriction in the rat lung in situ
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DOI：
10.1161/hh1301.093616
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发表时间：
2001-07-06
影响因子：
20.1
通讯作者：
Evans, AM
中科院分区：
文献类型：
--
作者：
Dipp, M;Evans, AM
缺氧性肺血管收缩(HPV)是肺动脉特有的，它有助于呼吸/灌流匹配。然而，在肺气肿等疾病中，HPV可以促进缺氧性肺动脉高压。我们最近发现，低氧通过增加循环ADP-核糖(CADPR)在平滑肌中的积聚，从而通过兰尼定受体释放钙来部分地收缩肺动脉。我们现在报道cADPR在大鼠离体肺动脉和大鼠在体肺HPV中的作用。在离体肺动脉上，经膜的cADPR拮抗剂8-bromo-cADPR可阻断肌浆网对兰尼定敏感的平滑肌钙离子释放，从而阻断持续的HPV，最重要的是，我们发现8-bromo-cADPR可阻断大鼠在体肺泡缺氧所致的HPV。HPV的抑制不影响(1)膜去极化和电压门控钙内流的收缩，(2)内皮源性血管收缩的释放，或(3)内皮依赖性的血管收缩。我们的研究结果表明，HPV既是由cADPR在大鼠肺内触发的，也是由cADPR在肺内维持的。
Hypoxic pulmonary vasoconstriction (HPV) is unique to pulmonary arteries, and it aids ventilation/perfusion matching. However, in diseases such as emphysema, HPV can promote hypoxic pulmonary hypertension. We recently showed that hypoxia constricts pulmonary arteries in part by increasing cyclic ADP-ribose (cADPR) accumulation in the smooth muscle and, thereby, Ca2+ release by ryanodine receptors. We now report on the role of cADPR in HPV in isolated rat pulmonary arteries and in the rat lung in situ. In isolated pulmonary arteries, the membrane-permeant cADPR antagonist, 8-bromo-cADPR, blocked sustained HPV by blocking Ca2+ release from smooth muscle ryanodine-sensitive stores in the sarcoplasmic reticulum, Most importantly, we showed that 8-bromo-cADPR blocks HPV induced by alveolar hypoxia in the ventilated rat lung in situ. Inhibition of HPV was achieved without affecting (1) constriction by membrane depolarization and voltage-gated Ca2+ influx, (2) the release (by hypoxia) of an endothelium-derived vasoconstrictor, or (3) endothelium-dependent vasoconstriction. Our findings suggest that HPV is both triggered and maintained by cADPR in the rat lung in situ.