首页> 外文期刊>American Journal of Physiology >The endocannabinoid arachidonyl ethanolamide (anandamide) increases pulmonary arterial pressure via cyclooxygenase-2 products in isolated rabbit lungs.
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The endocannabinoid arachidonyl ethanolamide (anandamide) increases pulmonary arterial pressure via cyclooxygenase-2 products in isolated rabbit lungs.

机译:内源性大麻素花生四烯酸乙醇酰胺(anandamide)通过离体兔肺中的环氧合酶2产物增加肺动脉压。

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摘要

Several cannabinoids elicit systemic vasodilation, mainly via CB1 cannabinoid and vanilloid receptors. However, effects in the pulmonary circulation are unknown. Using the isolated, ventilated, buffer-perfused rabbit lung, we have shown that the endocannabinoids arachidonyl ethanolamide (anandamide) and 2-arachidonyl glycerol (2-AG) dose-dependently increase pulmonary arterial pressure (+19.9 +/- 3.4 mmHg, 5 microM, and +39.5 +/- 10.8 mmHg, 0.4 microM, respectively). 2-AG induced lung edema. The CB1 receptor antagonist AM-251 (0.1 and 5 microM) and the VR1 vanilloid receptor antagonist capsazepine (10 microM) failed to reduce anandamide's effects. The metabolically stable anandamide and 2-AG analogs R-methanandamide and noladin ether, Delta9-tetrahydrocannabinol, and the synthetic cannabinoid HU-210, which is no arachidonic acid product, were without effect. The unspecific cyclooxygenase (COX) inhibitor aspirin (100 microM, P < 0.001) and the specific COX-2 inhibitor nimesulide (10 microM, P < 0.01) completely prevented pulmonary hypertension after 5 microM anandamide. COX-2 RNA was detected in rabbit lungs. The synthetic thromboxane receptor antagonist SQ 29,548 was without effect, but the specific EP1 prostanoid receptor antagonist SC-19220 (100 microM) inhibited the pressure increase after anandamide (P < 0.05). PCR analysis detected fatty acid amidohydrolase (FAAH), an enzyme that degrades endocannabinoids, in rabbit lung tissue. Furthermore, the specific FAAH inhibitor methyl arachidonyl fluorophosphonate (0.1 microM) blocked pressure effects of anandamide (P < 0.01). Finally, anandamide (99 +/- 55 pmol/g) and 2-AG (19.6 +/- 8.4 nmol/g) were found in native lungs. We conclude that anandamide increases pulmonary arterial pressure via COX-2 metabolites following enzymatic degradation by FAAH into arachidonic acid products.
机译:几种大麻素主要通过CB1大麻素和香草素受体引起全身血管舒张。但是,对肺循环的影响尚不清楚。使用隔离的,通气的,缓冲液灌注的兔肺,我们已经证明内源性大麻素花生四烯酸乙醇酰胺(anandamide)和2-花生四烯酸甘油酯(2-AG)剂量依赖性地增加了肺动脉压(+19.9 +/- 3.4 mmHg,5 microM和+39.5 +/- 10.8 mmHg(分别为0.4 microM)。 2-AG引起肺水肿。 CB1受体拮抗剂AM-251(0.1和5 microM)和VR1香草受体拮抗剂capsazepine(10 microM)未能降低anandamide的作用。没有花生四烯酸产物的代谢稳定的阿南酰胺和2-AG类似物R-甲南酰胺和Noladin醚,Delta9-四氢大麻酚以及合成的大麻素HU-210,都没有作用。非特异性环氧合酶(COX)抑制剂阿司匹林(100 microM,P <0.001)和特异性COX-2抑制剂尼美舒利(10 microM,P <0.01)完全预防了5 microM阿南酰胺后的肺动脉高压。在兔肺中检测到COX-2 RNA。合成的血栓烷受体拮抗剂SQ 29,548没有作用,但是特定的EP1类前列腺素受体拮抗剂SC-19220(100 microM)抑制了金刚烷酰胺后的压力升高(P <0.05)。 PCR分析检测到兔肺组织中的脂肪酸酰胺水解酶(FAAH),一种降解内源性大麻素的酶。此外,特定的FAAH抑制剂花生四烯酸氟膦酸甲酯(0.1 microM)阻止了花生四烯酸酰胺的压力作用(P <0.01)。最后,在天然肺中发现了anandamide(99 +/- 55 pmol / g)和2-AG(19.6 +/- 8.4 nmol / g)。我们得出结论,在由FAAH酶促降解为花生四烯酸产品后,anandamide通过COX-2代谢物增加肺动脉压。

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