School of Life and Environmental Sciences, Deakin University, Geelong, Victoria, Australia.
Am J Physiol Regul Integr Comp Physiol. 2010 Mar;298(3):R767-75. doi: 10.1152/ajpregu.00148.2009. Epub 2010 Jan 13.
This study determined the role of nitric oxide (NO) in neurogenic vasodilation in mesenteric resistance arteries of the toad Bufo marinus. NO synthase (NOS) was anatomically demonstrated in perivascular nerves, but not in the endothelium. ACh and nicotine caused TTX-sensitive neurogenic vasodilation of mesenteric arteries. The ACh-induced vasodilation was endothelium-independent and was mediated by the NO/soluble guanylyl cyclase signaling pathway, inasmuch as the vasodilation was blocked by the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and the NOS inhibitors N(omega)-nitro-l-arginine methyl ester and N(omega)-nitro-l-arginine. Furthermore, the ACh-induced vasodilation was significantly decreased by the more selective neural NOS inhibitor N(5)-(1-imino-3-butenyl)-l-ornithine. The nicotine-induced vasodilation was endothelium-independent and mediated by NO and calcitonin gene-related peptide (CGRP), inasmuch as pretreatment of mesenteric arteries with a combination of N(omega)-nitro-l-arginine and the CGRP receptor antagonist CGRP-(8-37) blocked the vasodilation. Clotrimazole significantly decreased the ACh-induced response, providing evidence that a component of the NO vasodilation involved Ca(2+)-activated K(+) or voltage-gated K(+) channels. These data show that NO control of mesenteric resistance arteries of toad is provided by nitrergic nerves, rather than the endothelium, and implicate NO as a potentially important regulator of gut blood flow and peripheral blood pressure.
本研究旨在确定一氧化氮（NO）在蟾蜍肠系膜阻力动脉的神经源性血管舒张中的作用。NO 合酶（NOS）在血管周围神经中存在，但不在内皮细胞中存在。乙酰胆碱（ACh）和尼古丁引起肠系膜动脉的 TTX 敏感的神经源性血管舒张。ACh 诱导的血管舒张是内皮细胞非依赖性的，是由 NO/可溶性鸟苷酸环化酶信号通路介导的，因为血管舒张被可溶性鸟苷酸环化酶抑制剂 1H-[1,2,4]恶二唑[4,3-a]喹喔啉-1-酮和 NOS 抑制剂 N(ω)-硝基-L-精氨酸甲酯和 N(ω)-硝基-L-精氨酸阻断。此外，ACh 诱导的血管舒张被更具选择性的神经 NOS 抑制剂 N(5)-(1-亚氨基-3-丁烯基)-L-鸟氨酸显著降低。尼古丁诱导的血管舒张是内皮细胞非依赖性的，由 NO 和降钙素基因相关肽（CGRP）介导，因为用 N(ω)-硝基-L-精氨酸和 CGRP 受体拮抗剂 CGRP-(8-37) 的组合预处理肠系膜动脉可阻断血管舒张。克霉唑显著降低了 ACh 诱导的反应，这提供了证据表明，NO 血管舒张的一个组成部分涉及 Ca(2+)-激活的 K(+)或电压门控的 K(+)通道。这些数据表明，NO 对蟾蜍肠系膜阻力动脉的控制是由 nitrergic 神经提供的，而不是内皮细胞，并且暗示 NO 作为肠道血流和外周血压的潜在重要调节剂。
