Zygmunt P M, Ryman T, Högestätt E D
Department of Clinical Pharmacology, Lund University, Sweden.
Acta Physiol Scand. 1995 Nov;155(3):257-66. doi: 10.1111/j.1748-1716.1995.tb09972.x.
Relaxant effects of acetylcholine (ACh), histamine, calcitonin gene-related peptide (CGRP) and the calcium ionophore A23187 were examined in rat femoral (phi approximately 0.2 mm), mesenteric (0.2 mm), intrarenal (0.2 mm) and hepatic (0.3 mm) arteries, and aorta (2 mm). Acetylcholine elicited an endothelium-dependent relaxation in all arteries. Histamine induced an endothelium-dependent relaxation in aorta, and mesenteric and intrarenal arteries, whereas a partly endothelium-dependent and mainly endothelium-independent relaxation was observed in hepatic and femoral arteries, respectively. In hepatic, mesenteric and intrarenal arteries, CGRP induced an endothelium-independent relaxation, whereas either small or no relaxation was obtained in aorta and femoral arteries respectively. A23187 induced an endothelium-dependent relaxation in the aorta and hepatic artery, whereas A23187 had no relaxant effect in femoral, mesenteric and intrarenal arteries. N omega-nitro-L-arginine (L-NOARG, 0.3 mM) reduced the maximum ACh-induced relaxation (in the presence of 10 microM indomethacin) by 66% in the aorta, and abolished the relaxation in femoral and intrarenal arteries. A marked L-NOARG/indomethacin-resistant relaxation was obtained in mesenteric and hepatic arteries. Levcromakalim induced a concentration-dependent and almost complete relaxation in all arteries. When contracted by a 60 mM K+ solution, all arteries responded to ACh with a relaxation that was abolished by L-NOARG. These results demonstrate marked regional differences with regard to the vascular effects of ACh, histamine, CGRP and A23187. Whereas nitric oxide appears to mediate endothelium-dependent relaxation regardless of the vascular region, an L-NOARG/indomethacin-resistant relaxation, presumably mediated by an endothelium-deprived hyperpolarizing factor, was observed only in mesenteric and hepatic arteries, and aorta.
在大鼠股动脉（直径约0.2毫米）、肠系膜动脉（0.2毫米）、肾内动脉（0.2毫米）、肝动脉（0.3毫米）和主动脉（2毫米）中检测了乙酰胆碱（ACh）、组胺、降钙素基因相关肽（CGRP）和钙离子载体A23187的舒张作用。乙酰胆碱在所有动脉中均引起内皮依赖性舒张。组胺在主动脉、肠系膜动脉和肾内动脉中诱导内皮依赖性舒张，而在肝动脉和股动脉中分别观察到部分内皮依赖性和主要非内皮依赖性舒张。在肝动脉、肠系膜动脉和肾内动脉中，CGRP诱导非内皮依赖性舒张，而在主动脉和股动脉中分别获得较小或无舒张作用。A23187在主动脉和肝动脉中诱导内皮依赖性舒张，而A23187在股动脉、肠系膜动脉和肾内动脉中无舒张作用。Nω-硝基-L-精氨酸（L-NOARG，0.3 mM）使主动脉中最大ACh诱导的舒张（在存在10μM吲哚美辛的情况下）降低了66%，并消除了股动脉和肾内动脉中的舒张。在肠系膜动脉和肝动脉中获得了明显的L-NOARG/吲哚美辛抗性舒张。左旋克罗卡林在所有动脉中诱导浓度依赖性且几乎完全的舒张。当用60 mM K+溶液收缩时，所有动脉对ACh的舒张反应均被L-NOARG消除。这些结果表明，ACh、组胺、CGRP和A23187的血管效应存在明显的区域差异。尽管一氧化氮似乎介导了内皮依赖性舒张，而与血管区域无关，但仅在肠系膜动脉、肝动脉和主动脉中观察到了可能由内皮缺失的超极化因子介导的L-NOARG/吲哚美辛抗性舒张。
