肾上腺髓质素诱导离体犬视网膜动脉舒张的机制

Mechanism of adrenomedullin-induced relaxation in isolated canine retinal arteries.

作者信息

Okamura T, Ayajiki K, Kangawa K, Toda N

机构信息

Department of Pharmacology, Shiga University of Medical Science, Ohtsu, Japan.

出版信息

Invest Ophthalmol Vis Sci. 1997 Jan;38(1):56-61.

PMID:9008630

Abstract

PURPOSE

To analyze the mechanism of action of adrenomedullin (AM), a peptide recently isolated from human pheochromocytoma, in isolated canine central retinal arteries and to compare the action of calcitonin gene-related peptide (CCRP).

METHODS

Changes in isometric tension were recorded in helical strips of the arteries with and without the endothelium.

RESULTS

Both AM and CGRP produced relaxation: EC50s were 2.62 and 0.71 x 10(-9) mol/l, respectively, and maximal relaxations were 85.1% and 84.3%, respectively. The AM-induced relaxation was endothelium-independent and unaffected by indomethacin, Ng-nitro-L-arginine, methylene blue, and glibencaalmide. Treatment with [8-37] CGRP markedly inhibited the relaxations caused by AM and CGRP. Treatment with a high concentration of sodium nitroprusside abolished the relaxation caused by nitroglycerin and atrial natriuretic peptide and reduced the relaxation caused by AM and CGRP. A high concentration of beraprost, a stable analog of prostaglandin I2, suppressed the response to AM and CGRP but not to nitroglycerin.

CONCLUSIONS

Endothelium-independent relaxations to AM of canine retinal arteries may be mediated primarily by intracellular cyclic adenosine monophosphate by stimulation of CGRP1 receptors and partially by cyclic guanosine monophosphate; cyclic guanosine monophosphate is unlikely ot be produced by methylene blue-sensitive soluble guanylate cyclase. Prostanoids, nitric oxide, and adenosine triphosphate-dependent K+ channel opening do not appear to be involved in the AM-induced relaxation.

摘要

目的

分析最近从人嗜铬细胞瘤中分离出的一种肽——肾上腺髓质素（AM）在离体犬视网膜中央动脉中的作用机制，并比较其与降钙素基因相关肽（CGRP）的作用。

方法

记录有内皮和无内皮的动脉螺旋条带的等长张力变化。

结果

AM和CGRP均引起舒张：半数有效浓度（EC50）分别为2.62和0.71×10⁻⁹mol/L，最大舒张率分别为85.1%和84.3%。AM诱导的舒张不依赖于内皮，且不受吲哚美辛、Nω-硝基-L-精氨酸、亚甲蓝和格列本脲的影响。用[8-37]CGRP处理可显著抑制AM和CGRP引起的舒张。用高浓度硝普钠处理可消除硝酸甘油和心房利钠肽引起的舒张，并降低AM和CGRP引起的舒张。高浓度的贝前列素（一种前列腺素I2的稳定类似物）可抑制对AM和CGRP的反应，但不抑制对硝酸甘油的反应。