Mesenteric vasodilation mediated by endothelial anandamide receptors.
Mesenteric vasodilation mediated by endothelial anandamide receptors.
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由内皮 anandamide 受体介导的肠系膜血管舒张。
DOI：
10.1161/01.hyp.33.1.429
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Kunos,G
中科院分区：
文献类型：
--
作者：
Wagner,JA;Varga,K;Járai,Z;Kunos,G
- 大麻素，包括内源性配体花生四烯酸乙醇酰胺（arachidonyl ethanolamide），通过激活位于外周的CB 1大麻素受体引起大鼠明显的低血压，这也与内毒素（脂多糖[LPS]）诱导的低血压有关。本研究旨在测试血管CB 1受体在大麻素和内毒素诱导的肠系膜血管舒张中的作用。在离体缓冲液灌注的大鼠肠系膜动脉床中，anandamide诱导持续时间长（长达60分钟）的剂量依赖性血管舒张（ED 50：79±3 nmol;最大舒张：77±2%），可被0.5 - 5.0 μmol/L的选择性CB 1受体拮抗剂SR 141716 A抑制。低剂量的钙离子载体离子霉素也引起了SR 141716 A抑制的肠系膜血管舒张。代谢稳定的类似物R-甲烟酰胺引起肠系膜血管舒张（ED 50：286±29 nmol），而强效合成CB 1受体激动剂WIN 55212-2和HU-210分别未引起血管张力变化或仅引起不受SR 141716 A影响的轻微扩张作用。内源性配体2-花生四烯酸甘油不引起血管张力的变化，而Δ9-四氢大麻酚和花生四烯酸引起肠系膜血管收缩。内皮剥脱后，扩张剂对花生四烯酸的反应略有降低，不再受SR 141716 A抑制。在LPS预处理大鼠的制剂中，单独使用SR 141716 A可导致灌注压显著延长，而在有或无LPS的体外灌注对照制剂中或在LPS预处理大鼠的内皮剥脱后，SR 141716 A无此类作用。我们的结论是，anandamide诱导的肠系膜血管舒张是由位于内皮的SR 141716 A敏感的“anandamide受体”介导的，不同于CB 1大麻素受体，这种受体的激活由内源性大麻素，可能anandamide，有助于LPS诱导的肠系膜血管舒张在体内。
—Cannabinoids, including the endogenous ligand anandamide (arachidonyl ethanolamide), elicit pronounced hypotension in rats via activation of peripherally located CB1 cannabinoid receptors, which have been also implicated in endotoxin (lipopolysaccharide [LPS])-induced hypotension. The present study was designed to test the role of vascular CB1 receptors in cannabinoid- and endotoxin-induced mesenteric vasodilation. In the isolated, buffer-perfused rat mesenteric arterial bed precontracted with phenylephrine, anandamide induced long-lasting (up to 60 minutes) dose-dependent vasodilation (ED50: 79±3 nmol; maximal relaxation: 77±2%), inhibited by 0.5 to 5.0 μmol/L of the selective CB1 receptor antagonist SR141716A. Low doses of the calcium ionophore ionomycin also caused mesenteric vasodilation inhibited by SR141716A. The metabolically stable analogue R-methanandamide elicited mesenteric vasodilation (ED50: 286±29 nmol), whereas the potent synthetic CB1 receptor agonists WIN 55212-2 and HU-210 caused no change in vascular tone or only a minor dilator effect not affected by SR141716A, respectively. The endogenous ligand 2-arachidonyl glycerol caused no change in vascular tone, whereas Δ9-tetrahydrocannabinol and arachidonic acid caused mesenteric vasoconstriction. After endothelial denudation, the dilator response to anandamide was slightly reduced and was no longer inhibited by SR141716A. In preparations from LPS-pretreated rats, SR141716A alone caused a significant and prolonged increase in perfusion pressure, whereas it had no such effect in control preparations perfused in vitro with or without LPS or after endothelial denudation in preparations from rats pretreated with LPS. We conclude that anandamide-induced mesenteric vasodilation is mediated by an endothelially located SR141716A-sensitive “anandamide receptor” distinct from CB1 cannabinoid receptors and that activation of such receptors by an endocannabinoid, possibly anandamide, contributes to LPS-induced mesenteric vasodilation in vivo.
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影响因子：
64.8
作者：
PARNAVELAS, JG;KELLY, W;BURNSTOCK, G
通讯作者：
BURNSTOCK, G
影响因子：
5
作者：
Calignano, A;LaRana, G;Piomelli, D
通讯作者：
Piomelli, D
DOI：
--
发表时间：
1996-09
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
V. Showalter;D. R. Compton;Billy R. Martin;M. Abood
通讯作者：
V. Showalter;D. R. Compton;Billy R. Martin;M. Abood
DOI：
10.1006/bbrc.1998.8187
发表时间：
1998-02-24
影响因子：
3.1
作者：
Sugiura, T;Kodaka, T;Waku, K
通讯作者：
Waku, K
影响因子：
3.8
作者：
Schatz, AR;Lee, M;Kaminski, NE
通讯作者：
Kaminski, NE