Genomic characteristics of pulmonary circulation in high-altitude living animal

本研究从eNOS、DDAH(二甲基精氨酸二甲氨基水解酶)、ADMA(不对称甲基化精氨酸)和ET-1等与低氧有关的基因组产物方面研究了耐低氧所致肺高压的高原适应动物--牦牛、肺心病的肺组织特征。结果：1.牦牛肺组织eNOS、DDAH的蛋白表达和活性均高于对照牛。但是，两种动物肾脏中DDAH的蛋白表达程度是相同的。牦牛血浆ADMA水平是奶牛的5倍。在奶牛群体中，高海拔奶牛群体的ADMA水平是低海拔奶牛群体的4倍。牦牛血浆ET-1水平高于奶牛，说明野牦牛肺较牛肺eNOS蛋白表达增强，DDAH活性增强。相反，动物血浆ADMA和ET-1水平升高，表明血管扩张剂和血管收缩剂的平衡被上调。虽然我们没有评估血浆ADMA和ET-1的跨肺差异，但似乎牦牛肺优先表达保护性NO机制(S)，这可能是导致高海拔地区肺动脉压相对较低的原因。从发病机制和治疗策略上思考临床上对低氧空气所致的肺动脉高压和慢性呼吸衰竭的认识，可以从动物实验中得出一些有益的启示。

We investigated the pulmonary characteristics of Yak, a high-altitude adapted animal that is resistant to hypoxia-induced pulmonary hypertension, cor pulmonale in terms of hypoxia-responsible genomic products such as eNOS, DDAH (dimethylarginine dimethylaminohydrolase), ADMA (asymmetrically methylated Arginine) and ET-1.Results;1. The protein expression of eNOS, and protein expression and activity of DDAH in yak's lung tissue were more elevated than that of control cow. However, the degree of protein expression of DDAH in the Kidney was the same in both animals.2. The plasma level of ADMA was 5-times higher in Yak compared to that of cow. Among cow groups, high-altitude living one has 4-times high ADMA level compared to that of low-altitude living one.3. The plasma ET-1 level was higher in Yak than in cow.These results suggest that wild yak's lung has augmented eNOS protein and augmented DDAH activity compared to cow. On the contrary, the animal has elevated plasma ADMA and ET-1 suggesting that the balance of vasodilators and vasoconstrictors are up-regulated. Although we did not assess transpulmonary difference of plasma ADMA and ET-1, it appears that Yak's lung preferentially expressed protective NO mechanism(s) which may result the relatively low pulmonary arterial pressure despite of high-altitude. It may induce a good suggestion from the animal study if think about hypoxic-air induced pulmonary hypertension and chronic respiratory failure in clinical medicine in terms of pathogenesis and treatment strategy.