School of Nutrition and Health Promotion, Arizona State University, 401 E Tyler Mall, Mail Code 4501, Tempe, AZ, 85287-4501, USA.
J Comp Physiol B. 2013 Oct;183(7):959-67. doi: 10.1007/s00360-013-0757-0. Epub 2013 May 3.
For mammals, acetylcholine (ACh) promotes endothelium-dependent vasodilation primarily through nitric oxide (NO) and prostaglandin-mediated pathways, with varying reliance on endothelial-derived hyperpolarizing factors. Currently, no studies have been conducted on small systemic arteries from wild birds. We hypothesized that ACh-mediated vasodilation of isolated small arteries from mourning doves (Zenaida macroura) would likewise depend on endothelial-derived factors. Small resistance mesenteric and cranial tibial (c. tibial) arteries (80-150 μm, inner diameter) were cannulated and pre-constricted to 50 % of resting inner diameter with phenylephrine then exposed to increasing concentrations of ACh (10(-9)-10(-5) M) or the NO donor, sodium nitroprusside (SNP; 10(-12)-10(-3) M). For mesenteric arteries, ACh-mediated vasodilation was significantly blunted with the potassium channel antagonist tetraethylammonium chloride (TEA, 10 mM); whereas responses were only moderately impaired with endothelial disruption or inhibition of prostaglandins (indomethacin, 10 μM). In contrast, endothelial disruption as well as exposure to TEA largely abolished vasodilatory responses to ACh in c. tibial arteries while no effect of prostaglandin inhibition was observed. For both vascular beds, responses to ACh were moderately dependent on the NO signaling pathway. Inhibition of NO synthase had no impact, despite complete reversal of phenylephrine-mediated tone with SNP, whereas inhibition of soluble guanylate cyclase (sGC) caused minor impairments. Endothelium-independent vasodilation also relied on potassium channels. In summary, ACh-mediated vasodilation of mesenteric and c. tibial arteries occurs through the activation of potassium channels to induce hyperpolarization with moderate reliance on sGC. Prostaglandins likewise play a small role in the vasodilatory response to ACh in mesenteric arteries.
对于哺乳动物而言,乙酰胆碱(ACh)通过一氧化氮(NO)和前列腺素介导的途径促进内皮依赖性血管舒张,其中对内皮衍生的超极化因子的依赖程度有所不同。目前,尚未对野生鸟类的小型系统性动脉进行研究。我们假设,从哀鸽(Zenaida macroura)分离的小型动脉中 ACh 介导的血管舒张同样依赖于内皮衍生的因子。小阻力肠系膜和颅侧胫骨(c. tibial)动脉(80-150μm,内径)用酚妥拉明预收缩至静息内径的 50%,然后用不同浓度的 ACh(10(-9)-10(-5)M)或一氧化氮供体硝普钠(SNP;10(-12)-10(-3)M)进行处理。对于肠系膜动脉,钾通道拮抗剂四乙铵氯化物(TEA,10mM)显著减弱了 ACh 介导的血管舒张;而内皮破坏或前列腺素抑制(吲哚美辛,10μM)只会适度损害反应。相比之下,内皮破坏以及暴露于 TEA 几乎完全消除了 c. tibial 动脉对 ACh 的血管舒张反应,而前列腺素抑制没有效果。对于这两个血管床,ACh 的反应都中度依赖于 NO 信号通路。尽管 SNP 完全逆转了去甲肾上腺素介导的张力,但一氧化氮合酶的抑制没有影响,而可溶性鸟苷酸环化酶(sGC)的抑制则导致轻微的损害。内皮非依赖性血管舒张也依赖于钾通道。综上所述,肠系膜和 c. tibial 动脉中 ACh 介导的血管舒张是通过激活钾通道引起超极化来实现的,对 sGC 的依赖程度适中。前列腺素在肠系膜动脉对 ACh 的血管舒张反应中也起着较小的作用。