Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112-2699, USA.
Can J Physiol Pharmacol. 2012 Apr;90(4):485-500. doi: 10.1139/y2012-012. Epub 2012 Mar 27.
Peroxynitrite (PN) worsens pathological conditions associated with oxidative stress. However, beneficial effects have also been reported. PN has been shown to demonstrate vasodilator as well as vasoconstrictor properties that are dependent upon the experimental conditions and the vascular bed studied. PN-induced vascular smooth muscle relaxation may involve the formation of nitric oxide (NO) donors. The present results show that PN has significant vasodilator activity in the pulmonary and systemic vascular beds, and that responses to PN were not attenuated by L-penicillamine (L-PEN), a PN scavenger, whereas responses to sodium nitroprusside (SNP) were decreased. PN had a small inhibitory effect on decreases in arterial pressure in response to the NO donors diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA/NO) and S-nitrosoglutathione (GSNO). PN partially reversed hypoxic pulmonary vasoconstriction. PN responses were attenuated by the soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and responses to PN and the PN precursor, 3-morpholinosydnonimine (SIN-1), were different. These data show that PN has potent pulmonary vasodilator activity in the rat, and provide evidence that a PN interaction with S-nitrosothiols is not the major mechanism mediating the response. These data suggest that responses to PN are mediated by the activation of sGC, and that PN has a small inhibitory effect on NO responses.
过氧亚硝酸盐（PN）会加重与氧化应激相关的病理状况。然而，也有报道称其具有有益的作用。PN 已被证明具有血管舒张剂和血管收缩剂的特性，这取决于实验条件和研究的血管床。PN 诱导的血管平滑肌松弛可能涉及一氧化氮（NO）供体的形成。本研究结果表明，PN 在肺和全身血管床中具有显著的血管扩张活性，且对 PN 的反应不受 PN 清除剂 L-青霉胺（L-PEN）的减弱，而对硝普钠（SNP）的反应则减弱。PN 对一氧化氮供体二乙氨乙基（Z）-1-（N，N-二乙基氨基）二氮烯-1,2-二醇（DEA/NO）和 S-亚硝基谷胱甘肽（GSNO）引起的动脉血压降低有较小的抑制作用。PN 部分逆转了低氧性肺血管收缩。可溶性鸟苷酸环化酶（sGC）抑制剂 1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ）可减弱 PN 反应，且 PN 与 PN 前体 3-吗啉基-sydnonimine（SIN-1）的反应不同。这些数据表明，PN 在大鼠中具有强大的肺血管扩张活性，并提供证据表明，PN 与 S-亚硝基硫醇的相互作用不是介导反应的主要机制。这些数据表明，PN 对 sGC 的激活具有反应性，且 PN 对 NO 反应具有较小的抑制作用。
