Zaobornyj Tamara, Valdez Laura B, Iglesias Darío E, Gasco Manuel, Gonzales Gustavo F, Boveris Alberto
Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
Am J Physiol Heart Circ Physiol. 2009 Jun;296(6):H1741-7. doi: 10.1152/ajpheart.00422.2008. Epub 2009 Apr 3.
Rats submitted to high altitude (Cerro de Pasco, Perú, 4,340 m, Po(2) = 12.2 kPa) for up to 84 days showed a physiological adaptive response with decreased body weight gain (15%), increased right ventricle weight (100%), and increased hematocrit (40%) compared with sea level animals. These classical parameters of adaptation to high altitude were accompanied by an increase in heart mitochondrial enzymes: complexes I-III activity by 34% and mitochondrial nitric oxide synthase (mtNOS) activity and expression by >75%. The hyperbolic increase for mtNOS activity during adaptation to high altitude was similar to the observed pattern for hematocrit. Hematocrit and mtNOS activity mean values correlated linearly (r(2) = 0.75, P <or= 0.05). Chronic treatment for 28 days with sildenafil (50 mgkg(-1).day(-1)) decreased the response of mtNOS to high altitude by 25%. Conversely, N(G)-nitro-l-arginine methyl ester treatment (8.3 mgkg(-1)day(-1)) increased such response by 40%, whereas l-arginine treatment (106 mgkg(-1)*day(-1)) had no effect. Nitric oxide (NO) production by mtNOS accounts for approximately 49% of total cellular NO production in sea level rats and for approximately 54% in rats exposed to high altitude for 84 days. It is concluded that mtNOS is a substantial source of cardiac NO, a factor in the adaptive response to sustained heart hypoxia that is susceptible to be modified by pharmacological treatments.
暴露于高海拔环境（秘鲁塞罗德帕斯科，4340米，Po₂ = 12.2千帕）长达84天的大鼠与海平面动物相比，表现出一种生理适应性反应，体重增加减少（15%），右心室重量增加（100%），血细胞比容增加（40%）。这些适应高海拔的经典参数伴随着心脏线粒体酶的增加：复合体I - III活性增加34%，线粒体一氧化氮合酶（mtNOS）活性和表达增加超过75%。在适应高海拔过程中，mtNOS活性呈双曲线增加，与观察到的血细胞比容模式相似。血细胞比容和mtNOS活性平均值呈线性相关（r² = 0.75，P≤0.05）。用西地那非（50毫克·千克⁻¹·天⁻¹）进行28天的慢性治疗使mtNOS对高海拔的反应降低了25%。相反，N⁻硝基⁻L⁻精氨酸甲酯治疗（8.3毫克·千克⁻¹·天⁻¹）使这种反应增加了40%，而L⁻精氨酸治疗（106毫克·千克⁻¹·天⁻¹）则没有效果。mtNOS产生的一氧化氮（NO）在海平面大鼠的细胞总NO产生中约占49%，在暴露于高海拔84天的大鼠中约占54%。结论是，mtNOS是心脏NO的重要来源，是对持续性心脏缺氧适应性反应的一个因素，易受药物治疗的影响。
