Biotechnology Center, Federal University of Paraíba, PO Box 5009, 58.051-970 João Pessoa, PB, Brazil.
Eur J Pharmacol. 2012 Sep 5;690(1-3):170-5. doi: 10.1016/j.ejphar.2012.06.043. Epub 2012 Jul 14.
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 μM), a NO extracellular scavenger, and 1-H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one-ODQ (10 μM), an inhibitor of soluble guanylyl cyclase (sGC). In addition, the NDBP-induced relaxation was reduced by non-selective K(+) channels blocker KCl (20 mM) or selective K(+) channels blockers such as tetraethylammonium-TEA (B(KCa), 1 mM), charybdotoxin-ChTX (B(KCa), 100 nM), glibenclamide (K(ATP), 1μM) and 4-aminopyridine-4-AP (K(V), 1mM). In preparations with ODQ (10 μM) 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.
一氧化氮（NO）的生成减少与心血管疾病有关。因此，像有机硝酸盐这样的 NO 供体可用于治疗这些疾病。2-硝酸盐-1,3-二丁氧基丙烷（NDBP）是一种从甘油合成的有机硝酸盐，其药理作用尚未得到研究。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。在预先用苯肾上腺素收缩的动脉环中，NDBP（10(-8)-10(-4)M）引起浓度依赖性和内皮非依赖性舒张，该舒张作用被羟钴胺-HDX（30 μM），一种 NO 细胞外清除剂，以及 1-H-[1,2,4]恶二唑[4,3-a]喹喔啉-1-酮-ODQ（10 μM），一种可溶性鸟苷酸环化酶（sGC）抑制剂减弱。此外，NDBP 诱导的舒张作用被非选择性 K(+)通道阻滞剂 KCl（20 mM）或选择性 K(+)通道阻滞剂如四乙铵-TEA（B(KCa)，1 mM）、巴拉汀-ChTX（B(KCa)，100 nM）、格列本脲（K(ATP)，1μM）和 4-氨基吡啶-4-AP（K(V)，1mM）减弱。在含有 ODQ（10 μM）和 TEA（1 mM）的制剂中，反应几乎被消除。在大鼠平滑肌细胞培养物中，NDBP（10(-6)-10(-4)M）引起 NO 水平的浓度依赖性增加。这些发现表明，NDBP 通过 NO 生成和激活 sCG/cGMP/PKG 途径引起血管舒张。
