Regulation of rat intrapulmonary arterial tone by arachidonic acid and prostaglandin E2 during hypoxia.
Regulation of rat intrapulmonary arterial tone by arachidonic acid and prostaglandin E2 during hypoxia.
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缺氧时花生四烯酸和前列腺素 E2 对大鼠肺内动脉张力的调节
DOI：
10.1371/journal.pone.0073839
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gu Y
中科院分区：
文献类型：
--
作者：
Yan G;Wang Q;Shi H;Han Y;Ma G;Tang C;Gu Y
花生四烯酸（AA）及其代谢产物花生四烯酸（PG）参与调节血管张力和血管壁张力等血管稳态，但其在低氧性肺血管收缩（HPV）中的作用尚不清楚。在这项研究中，我们研究了AA和前列腺素E_2对大鼠离体肺内动脉（IPAs）缺氧反应的影响。方法与结果采用血管张力测量法对IPAs进行了调查。异汉防己甲素（20 µM）显著抑制缺氧性血管收缩的I相、IIb相和IIc相。吲哚美辛（100 µM）和NS 398均减弱KPSS诱导的血管收缩和HPV的I相、IIb相和IIc相，表明考克斯-2在大鼠IPA的缺氧反应中起主要作用。PGE 2单独引起了显着的血管收缩在分离的大鼠IPAs。这种收缩是由EP 4介导的。L-161982（1 µM）阻断EP 4可显著抑制缺氧性血管收缩的I相、IIb相和IIc相。然而，EP 1、EP 2、EP 3和DP 1受体拮抗剂AH 6809（3 μM）对KPSS或缺氧诱导的血管收缩无影响。Forskolin增加细胞内cAMP可显著减少KPSS引起的血管收缩，并可消除HPV I、II B和II c相。结论PGE 2对大鼠IPAs有明显的缩血管作用，这种作用可能是通过激活EP 4而实现的。此外，我们的研究结果表明，细胞内cAMP在调节血管张力中起着双重作用，这取决于cAMP的空间分布及其与EP受体和Ca ~（2+）通道的耦合。
Aims Arachidonic acid (AA) and its metabolites, prostaglandins (PG) are known to be involved in regulation of vascular homeostasis including vascular tone and vessel wall tension, but their potential role in Hypoxic pulmonary vasoconstriction (HPV) remains unclear. In this study, we examined the effects of AA and PGE2 on the hypoxic response in isolated rat intrapulmonary arteries (IPAs). Methods and Results We carried out the investigation on IPAs by vessel tension measurement. Isotetrandrine (20 µM) significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. Both indomethacin (100 µM) and NS398 attenuated KPSS-induced vessel contraction and phase I, phase IIb and phase IIc of HPV, implying that COX-2 plays a primary role in the hypoxic response of rat IPAs. PGE2 alone caused a significant vasoconstriction in isolated rat IPAs. This constriction is mediated by EP4. Blockage of EP4 by L-161982 (1 µM) significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. However, AH6809 (3 µM), an antagonist of EP1, EP2, EP3 and DP1 receptors, exerted no effect on KPSS or hypoxia induced vessel contraction. Increase of cellular cAMP by forskolin could significantly reduce KPSS-induced vessel contraction and abolish phase I, phase II b and phase II c of HPV. Conclusion Our results demonstrated a vasoconstrictive effect of PGE2 on rat IPAs and this effect is via activation of EP4. Furthermore, our results suggest that intracellular cAMP plays dual roles in regulation of vascular tone, depending on the spatial distribution of cAMP and its coupling with EP receptor and Ca2+ channels.