Calcitonin gene-related peptide-dependent vascular relaxation of rat aorta - An additional mechanism for nitroglycerin
Calcitonin gene-related peptide-dependent vascular relaxation of rat aorta - An additional mechanism for nitroglycerin
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DOI：
10.1016/s0006-2952(00)00290-2
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发表时间：
2000-06-15
影响因子：
5.8
通讯作者：
Fung, HL
中科院分区：
文献类型：
--
作者：
Booth, BP;Tabrizi-Fard, MA;Fung, HL
我们研究了降钙素基因相关肽(CGRP)在一氧化氮(NO)供体的血管扩张机制中的作用。通过将这些药物与选择性CGRP受体拮抗剂CGRP(8-37)孵育，以确定CGRP在NO供体引起的大鼠离体主动脉环扩张中的作用。CGRP(8-37)(0.63mU)引起硝酸甘油(NTG)、Piloty酸(PA)和SIN-1(Linsidomine)的血管扩张量效曲线右移。NTG、PA和SIN-1的EC(50)值分别增加8.3、5.2和2.3倍(P<；0.05)。用放射免疫法测定NTG和PA对大鼠主动脉CGRP释放的影响。大鼠主动脉与NTG或PA孵育30min后，降钙素基因相关肽释放分别增加189.5和214.6%(P<0.05)。CGRP(8-37)对硝普钠(SNP)、S-亚硝基乙酰青霉胺(SNAP)、四硝基甲烷(TnM)、二乙胺-NO复合体(DEA-NO)和二乙三胺/一氧化氮加合物(DETA NOate)的量效曲线无明显抑制作用(P>；0.05)。没有供体与主动脉条孵育，单独使用NTG和PA可显著诱导非代谢物羟胺的形成(分别为232.4%和364.9%，P<；0.05)。这些结果表明，只有NTG和PA和较小程度的SIN-1刺激大鼠主动脉释放CGRP，这随后参与了这些药物的血管扩张活动。羟胺的形成表明NO的产生与血管壁上CGRP的释放之间可能存在联系。(C)2000年爱思唯尔科学公司。
We investigated the involvement of calcitonin gene-related peptide (CGRP) in the vasodilatory mechanism of action of nitric oxide (NO) donors. The functional role of CGRP in NO donor-induced vasodilation of isolated rat aortic rings was determined by incubating these drugs with and without CGRP(8-37), a selective CGRP receptor antagonist. CGRP(8-37) (0.63 mu M) induced rightward shifts in the vasodilatory concentration-response curves for nitroglycerin (NTG), Piloty's acid (PA), and SIN-1 (linsidomine). The Ec(50) values for NTG, PA, and SIN-1 were increased by 8.3-, 5.2-, and 2.3-fold, respectively (P < 0.05). The release of CGRP from rat aorta in response to NTG and PA was measured specifically by radioimmunoassay. Thirty-minute incubations of NTG or PA with rat aorta induced 189.5 and 214.6% increases, respectively, in CGRP release when compared with the control (P ( 0.05). The concentration-response curves of sodium nitroprusside (SNP), S-nitroso-acetylpenicillamine (SNAP), tetranitromethane (TNM), diethylamine NO complex (DEA-NO), and diethylenetriamine/nitric oxide adduct (DETA NONOate) were not inhibited significantly by CGRP(8-37) co-incubation (P > 0.05). NO donors also were incubated with aortic strips, and NTG and PA alone induced significant formation of hydroxylamine, a NO- metabolite (232.4 and 364.9%, respectively, P < 0.05). These results indicate that only NTG and PA, and to a lesser extent SIN-1, stimulate the release of CGRP from the rat aorta, which subsequently contributes to the vasodilatory activity of these agents. The hydroxylamine formation suggests a possible link between NO- generation and CGRP release from the vascular wall. (C) 2000 Elsevier Science Inc.