Wang X, Han C, Fiscus R R
Department of Physiology, Loyola University Medical Center, Maywood, Illinois 60153.
Neuropeptides. 1991 Oct;20(2):115-24. doi: 10.1016/0143-4179(91)90061-m.
Calcitonin gene-related peptide (CGRP), a neuropeptide found in nerves surrounding most blood vessels, is a potent hypotensive agent in both humans and rats. In isolated strips of rat thoracic aorta, CGRP has been reported to cause endothelium-dependent relaxation. To study the cellular and molecular mechanisms involved in CGRP-induced vasodilation, we investigated the roles of two second messengers, cyclic AMP and cyclic GMP, as potential mediators of the signal transduction mechanism leading to vasodilation in response to CGRP in rat aorta. In the present study, the abdominal aorta, rather than thoracic aorta, was used because of its higher content of endogenous CGRP and, therefore, the greater likelihood of regulation by CGRP in vivo. Each abdominal aortic ring was precontracted with norepinephrine (NE) at its EC50 concentration (10-20 nM). CGRP (3-300 nM) caused concentration-dependent relaxations (reducing the NE-induced contractions by 34%) that were completely dependent on endothelium. The relaxations in response to CGRP were correlated in a time- and concentration-dependent manner with increases in aortic levels of both cyclic AMP and cyclic GMP. CGRP (100 nM) caused significant elevations of cyclic AMP levels (1.4 to 3.2 pmol/mg protein, at 1 min) and cyclic GMP levels (1.6 to 3.6 pmol/mg protein, at 30 s). Like the vasorelaxant responses, both cyclic AMP and cyclic GMP responses to CGRP were totally dependent on the endothelium. Pre-incubation with indomethacin (3 microM, 15 min) did not alter cyclic AMP responses to CGRP (100 nM), suggesting that prostaglandins are not involved. Therefore, CGRP-induced vasodilations of abdominal aorta involve an endothelium-dependent mechanism associated with cyclic GMP elevations, similar to the mechanisms of vasodilation in response to acetylcholine and other endothelium-dependent vasodilators. However, CGRP-induced relaxations of aorta involve an additional mechanism (i.e., endothelium-dependent cyclic AMP elevations), which may also contribute to the intracellular mechanism of aortic vasodilation in response to CGRP.
降钙素基因相关肽（CGRP）是一种在大多数血管周围神经中发现的神经肽，在人类和大鼠中都是一种强效降压剂。据报道，在大鼠胸主动脉分离条中，CGRP可引起内皮依赖性舒张。为了研究CGRP诱导血管舒张所涉及的细胞和分子机制，我们研究了两种第二信使环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）作为大鼠主动脉中响应CGRP导致血管舒张的信号转导机制潜在介质的作用。在本研究中，使用腹主动脉而非胸主动脉，因为其内源CGRP含量较高，因此在体内受CGRP调节的可能性更大。每个腹主动脉环先用去甲肾上腺素（NE）以其半数有效浓度（10 - 20 nM）预收缩。CGRP（3 - 300 nM）引起浓度依赖性舒张（使NE诱导的收缩减少34%），且完全依赖于内皮。对CGRP的舒张反应与主动脉中cAMP和cGMP水平的升高呈时间和浓度依赖性相关。CGRP（100 nM）导致cAMP水平显著升高（1分钟时为1.4至3.2 pmol/mg蛋白）和cGMP水平显著升高（30秒时为1.6至3.6 pmol/mg蛋白）。与血管舒张反应一样，对CGRP的cAMP和cGMP反应都完全依赖于内皮。用吲哚美辛（3 microM，15分钟）预孵育不会改变对CGRP（100 nM）的cAMP反应，表明前列腺素不参与其中。因此，CGRP诱导的腹主动脉血管舒张涉及与cGMP升高相关的内皮依赖性机制，类似于对乙酰胆碱和其他内皮依赖性血管舒张剂的血管舒张机制。然而，CGRP诱导的主动脉舒张涉及另一种机制（即内皮依赖性cAMP升高），这也可能有助于主动脉对CGRP血管舒张的细胞内机制。
