Hao H, Fiscus R R, Wang X, Diana J N
Department of Physiology and Biophysics, Stroke Program Center of Excellence of Sanders-Brown Research Center on Aging, University of Kentucky College of Medicine, Lexington 40536-0230.
Neuropeptides. 1994 Feb;26(2):123-31. doi: 10.1016/0143-4179(94)90103-1.
Our previous studies showed that vasodilations and elevations of both cyclic AMP and cyclic GMP levels in rat aorta induced by rat calcitonin gene-related peptide (rCGRP) are inhibited by hemoglobin and methylene blue, blockers of the endothelium-derived relaxant factor (EDRF, now recognized as nitric oxide [NO]). In the present study, we used N omega-nitro-L-arginine (L-NNA), a selective inhibitor of nitric oxide synthase, to test whether rCGRP-induced relaxations and cyclic AMP and cyclic GMP responses in rat aorta require de novo synthesis of NO. L-NNA (30 microM, 15 min) inhibited by 84, 76 and 73% the relaxations induced by rCGRP at 1, 10 and 100 nM, respectively. D-NNA (30 microM), which does not inhibit nitric oxide synthase, did not block rCGRP-induced vasorelaxations. Addition of L-arginine (3 mM) 5 min before L-NNA completely prevented the L-NNA-inhibition of CGRP-induced relaxations. L-NNA (30 microM, 15 min) also inhibited the elevations of both cyclic AMP and cyclic GMP levels caused by CGRP (100 nM). The data suggest that de novo synthesis of nitric oxide from its precursor L-arginine is required for rCGRP to induce vasodilations and elevations of both cyclic AMP and cyclic GMP levels in rat aorta.
我们先前的研究表明，大鼠降钙素基因相关肽（rCGRP）诱导的大鼠主动脉血管舒张以及环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）水平升高，会受到血红蛋白和亚甲蓝的抑制，而血红蛋白和亚甲蓝是内皮源性舒张因子（EDRF，现认为是一氧化氮[NO]）的阻滞剂。在本研究中，我们使用一氧化氮合酶的选择性抑制剂Nω-硝基-L-精氨酸（L-NNA），来测试rCGRP诱导的大鼠主动脉舒张以及cAMP和cGMP反应是否需要从头合成NO。L-NNA（30微摩尔/升，15分钟）分别抑制了1纳摩尔、10纳摩尔和100纳摩尔rCGRP诱导的舒张作用的84%、76%和73%。不抑制一氧化氮合酶的D-NNA（30微摩尔/升）并未阻断rCGRP诱导的血管舒张。在加入L-NNA前5分钟添加L-精氨酸（3毫摩尔/升）可完全防止L-NNA对CGRP诱导舒张的抑制作用。L-NNA（30微摩尔/升，15分钟）也抑制了CGRP（100纳摩尔）引起的cAMP和cGMP水平升高。数据表明，rCGRP在大鼠主动脉中诱导血管舒张以及cAMP和cGMP水平升高需要从其前体L-精氨酸从头合成一氧化氮。
