The 2-nitrate-1,3-dibuthoxypropan, a new nitric oxide donor, induces vasorelaxation in mesenteric arteries of the rat
The 2-nitrate-1,3-dibuthoxypropan, a new nitric oxide donor, induces vasorelaxation in mesenteric arteries of the rat
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DOI：
10.1016/j.ejphar.2012.06.043
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发表时间：
2012-09-05
影响因子：
5
通讯作者：
Medeiros, Isac A.
中科院分区：
文献类型：
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作者：
Franca-Silva, Maria S.;Luciano, Melissa N.;Medeiros, Isac A.
一氧化氮 (NO) 可用性的降低与心血管疾病有关。因此，NO供体如有机硝酸盐可用于治疗这些疾病。 2-硝酸酯-1,3-二丁氧基丙烷（NDBP）是一种由甘油合成的有机硝酸酯，其药理作用尚未研究。在这项研究中，我们评估了 NDBP 对大鼠肠系膜上动脉的血管舒张作用。在去氧肾上腺素预收缩的动脉环中，NDBP (10(-8)-10(-4) M) 引起浓度依赖性和内皮依赖性舒张，这种舒张可被羟钴胺-HDX (30 μM)（一种 NO 细胞外清除剂）和 1-H-[1,2,4] 恶二唑[4,3-a] 减弱。 quinoxalin-1-one-ODQ (10 mu M)，一种可溶性鸟苷酸环化酶 (sGC) 抑制剂。此外，非选择性 K+ 通道阻滞剂 KCI (20 mM) 或选择性 K+ 通道阻滞剂如四乙铵-TEA (B-KCa, 1 mM)、charybdotoxin-ChTX (B-KCa, 100 nM)、格列本脲 (K-ATP, 1 muM) 和 4-aminopyridine-4-AP (K-V, 1 mM) 可减少 NDBP 诱导的松弛。毫米）。在使用 ODQ (10 μM) 加 TEA (1 mM) 的制剂中，反应几乎被消除。在大鼠平滑肌细胞培养中，NDBP (10(-6)-10(-4) M) 导致 NO 水平呈浓度依赖性增加。这些发现表明 NDBP 通过 NO 生成和 sCG/cGMP/PKG 途径激活引起血管舒张。 (C) 2012 Elsevier B.V. 保留所有权利。
The reduced availability of nitric oxide (NO) is associated with cardiovascular diseases. Therefore, NO donors such as organic nitrates are useful for the treatment of these disorders. The 2-nitrate-1,3-dibuthoxypropan (NDBP) is an organic nitrate synthesized from glycerin, which the pharmacological effects have not been investigated. In this study we evaluated the vasorelaxant effect induced by NDBP in superior mesenteric artery from rats. In phenylephrine pre-contracted artery rings, NDBP (10(-8)-10(-4) M) elicited concentration-dependent and endothelium-independent relaxation, which were attenuated by hydroxocobalamin-HDX (30 mu M), a NO extracellular scavenger, and 1-H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one-ODQ (10 mu M), an inhibitor of soluble guanylyl cyclase (sGC). In addition, the NDBP-induced relaxation was reduced by non-selective K+ channels blocker KCI (20 mM) or selective K+ channels blockers such as tetraethylammonium-TEA (B-KCa, 1 mM), charybdotoxin-ChTX (B-KCa, 100 nM), glibenclamide (K-ATP, 1 mu M) and 4-aminopyridine-4-AP (K-V, 1 mM). In preparations with ODQ (10 mu M) plus TEA (1 mM), the response was virtually abolished. In rat smooth muscle cells culture, NDBP (10(-6)-10(-4) M) caused concentration-dependent increases in NO levels. These findings suggest that NDBP causes vasorelaxation through NO generation and activation of the sCG/cGMP/PKG pathway. (C) 2012 Elsevier B.V. All rights reserved.