Analysis of responses to glyceryl trinitrate and sodium nitrite in the intact chest rat.
Analysis of responses to glyceryl trinitrate and sodium nitrite in the intact chest rat.
复制标题
DOI：
10.1016/j.niox.2012.03.009
复制
发表时间：
2012-05-15
期刊：
影响因子：
--
通讯作者：
Kadowitz PJ
中科院分区：
文献类型：
--
作者：
Nossaman BD;Pankey EA;Badejo AR Jr;Casey DB;Uppu S;Murthy SN;Kadowitz PJ
在完整胸部大鼠中比较了对硝酸甘油/硝酸甘油（GTN）、S-亚硝基谷胱甘肽（GSNO）和亚硝酸钠的反应。静脉注射GTN、亚硝酸钠和GSNO可使肺动脉压和体循环动脉压呈剂量依赖性降低。尽管心输出量没有减少，但肺动脉压和体动脉压的降低表明GTN、亚硝酸钠和GSNO在大鼠的肺血管和体血管床中具有显着的血管扩张活性。对GTN的反应被氨腈减弱，但不被别嘌呤醇减弱，而对GTN代谢形成的亚硝酸盐的反应被别嘌呤醇和氨腈减弱。别嘌呤醇和氰胺的结果表明，只有线粒体醛脱氢酶参与GTN，亚硝酸钠和GSNO的生物活化，而这两种途径都参与亚硝酸根阴离子在完整的大鼠的生物活化。血管扩张活性的比较表明，GSNO和GTN在降低大鼠肺动脉压和全身动脉压方面比亚硝酸钠有效1000倍以上。给予1H-[1，2，4]-恶二唑并[4，3-]喹喔啉-1-酮（ODQ）后，对GTN的反应显著减弱，表明反应是由可溶性鸟苷酸环化酶的活化介导的。这些数据表明，从GTN的代谢形成的一氧化氮的亚硝酸盐的减少，不能占血管扩张活性的GTN在完整的大鼠和另一种机制，也许形成的S-NO，可能介导的血管扩张反应GTN在这个物种。
Responses to glyceryl trinitrate/nitroglycerin (GTN), S-nitrosoglutathione (GSNO), and sodium nitrite were compared in the intact chest rat. The iv injections of GTN, sodium nitrite, and GSNO produced dose-dependent decreases in pulmonary and systemic arterial pressures. In as much as cardiac output was not reduced, the decreases in pulmonary and systemic arterial pressures indicate that GTN, sodium nitrite, and GSNO have significant vasodilator activity in the pulmonary and systemic vascular beds in the rat. Responses to GTN were attenuated by cyanamide, but not allopurinol, whereas responses to nitrite formed by the metabolism of GTN were attenuated by allopurinol and cyanamide. The results with allopurinol and cyanamide suggest that only mitochondrial aldehyde dehydrogenase is involved in the bioactivation of GTN, sodium nitrite, and GSNO, whereas both pathways are involved in the bioactivation of nitrite anion in the intact rat. The comparison of vasodilator activity indicates that GSNO and GTN are more than 1000 fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures in the rat. Following administration of 1H-[1,2,4]-oxadizaolo[4,3-]quinoxaline-1-one (ODQ), responses to GTN were significantly attenuated, indicating that responses are mediated by the activation of soluble guanylyl cyclase. These data suggest that the reduction of nitrite to nitric oxide formed from the metabolism of GTN, cannot account for the vasodilator activity of GTN in the intact rat and that another mechanism; perhaps the formation of an S-NO, may mediate the vasodilator response to GTN in this species.
登录
查看更多内容
DOI：
10.1073/pnas.74.8.3203
发表时间：
1977-01-01
影响因子：
11.1
作者：
ARNOLD, WP;MITTAL, CK;MURAD, F
通讯作者：
MURAD, F
DOI：
10.1152/ajpheart.01101.2009
发表时间：
2010-10-01
影响因子：
4.8
作者：
Badejo, Adeleke M., Jr.;Nossaman, Vaughn E.;Kadowitz, Philip J.
通讯作者：
Kadowitz, Philip J.
DOI：
10.1016/0304-4165(80)90297-4
发表时间：
1980-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
IGNARRO, LJ;GRUETTER, CA
通讯作者：
GRUETTER, CA
DOI：
10.1073/pnas.0503723102
发表时间：
2005-08-23
影响因子：
11.1
作者：
Chen, ZQ;Foster, MW;Stamler, JS
通讯作者：
Stamler, JS
影响因子：
3.5
作者：
IGNARRO, LJ;EDWARDS, JC;GRUETTER, CA
通讯作者：
GRUETTER, CA