Effect of chronic sodium nitrite therapy on monocrotaline-induced pulmonary hypertension.
Effect of chronic sodium nitrite therapy on monocrotaline-induced pulmonary hypertension.
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DOI：
10.1016/j.niox.2012.02.004
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发表时间：
2012-06-30
期刊：
影响因子：
--
通讯作者：
Kadowitz PJ
中科院分区：
文献类型：
--
作者：
Pankey EA;Badejo AM;Casey DB;Lasker GF;Riehl RA;Murthy SN;Nossaman BD;Kadowitz PJ
肺动脉高压（PH）是一种罕见的疾病，如果不进行治疗，会在3年内进行性并经常致命。PH的治疗包括使用多种药物和肺移植。虽然亚硝酸盐曾经被认为是内皮源性一氧化氮（NO）的无活性代谢产物，但越来越多的证据表明亚硝酸盐可能在PH的治疗中有用，但亚硝酸盐发挥其有益作用的机制仍不确定。本研究的目的是探讨慢性亚硝酸钠治疗在PH模型大鼠的影响。单次注射野百合碱60 mg;从第14天开始每天ip注射亚硝酸钠（3 mg/kg）并持续21天，当与具有野百合碱诱导的PH的未处理动物的值相比时，在第35天导致肺动脉压显著降低。在野百合碱处理的大鼠中，每天ip亚硝酸盐注射治疗21天，减少了右心室质量和小肺动脉的病理变化。亚硝酸盐治疗没有改变全身动脉压或心输出量的值时，在第35天测量。静脉注射硝普钠、亚硝酸钠和BAY 41-8543引起的肺动脉压降低在野百合碱诱导的肺动脉高压大鼠和慢性亚硝酸盐治疗的大鼠中与用U46619升高肺动脉压的动物中的反应相比没有差异。这些研究结果是一致的假设，即亚硝酸盐转化为血管活性NO，激活可溶性鸟苷酸环化酶和介导的血管舒张反应NO或NO衍生物的机制没有受损。目前的数据是一致的，与先前的研究结果在野百合碱诱导的PH中，全身动脉压和心输出量没有进行评估，并与假设，亚硝酸盐是有效的治疗野百合碱诱导的PH在啮齿动物是一致的。
Pulmonary hypertension (PH) is a rare disorder that without treatment is progressive and often fatal within 3 years. The treatment of PH involves the use of a diverse group of drugs and lung transplantation. Although nitrite was once thought to be an inactive metabolite of endothelial-derived nitric oxide (NO), there is increasing evidence that nitrite may be useful in the treatment of PH, but the mechanism by which nitrite exerts its beneficial effect remains uncertain. The purpose of this study was to investigate the effect of chronic sodium nitrite treatment in a PH model in the rat. Following induction of PH with a single injection of monocrotaline, 60 mg; daily ip injections of sodium nitrite (3 mg/kg) starting on day 14 and continuing for 21 days, resulted in a significantly lower pulmonary arterial pressure on day 35 when compared to values in untreated animals with monocrotaline-induced PH. In monocrotaline-treated rats, daily treatment with ip nitrite injections for 21 days decreased right ventricular mass and pathologic changes in small pulmonary arteries. Nitrite therapy did not change systemic arterial pressure or cardiac output when values were measured on day 35. The decreases in pulmonary arterial pressure in response to iv injections of sodium nitroprusside, sodium nitrite, and BAY 41-8543 were not different in rats with monocrotaline-induced pulmonary hypertension and rats with chronic nitrite therapy when compared to responses in animals in which pulmonary arterial pressure was increased with U46619. These findings are consistent with the hypothesis that the mechanisms that convert nitrite to vasoactive NO, activate soluble guanylyl cyclase and mediate the vasodilator response to NO or an NO derivative are not impaired. The present data are consistent with the results of a previous study in monocrotaline-induced PH in which systemic arterial pressure and cardiac output were not evaluated and are consistent with the hypothesis that nitrite is effective in the treatment of monocrotaline-induced PH in the rodent.
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