ADAPTATION TO CHRONIC HYPOXIA

适应慢性缺氧

• 批准号: 6118824
• 负责人: JOHN E BAKER
• 金额: $ 0.05万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6118824
• 关键词: bioengineering /biomedical engineering; biological products; biomaterials; biomedical resource; nucleic acids

Hypoxia from birth in immature rabbits increases the tolerance of isolated hearts to ischemia compared with age-matched normoxic controls. We determined if this increased tolerance was due to alterations in endogenous nitric oxide production. To test the hypothesis, rabbits (n=8/group) were raised from birth in a normoxic or hypoxic environment for 7-10 days and the hearts perfused with bicarbonate buffer. A nitric oxide donor S-nitrosoglutathione (GSNO) or a nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NAME) was added 15 min prior to a global ischemic period of 30 min, followed by 35 min reperfusion. GSNO (10 micromole/L) increased the recovery of left ventricular developed pressure in normoxic hearts to values not different from hypoxic hearts but had no effect on recovery of developed pressure in hypoxic hearts. L-NAME (200 micromole/L) completely abolished the cardioprotective effect of chronic hypoxia but had no effect on cardioprotection in norm oxic hearts. To determine if altered nitric oxide synthase (NOS) gene expression correlated with increased tolerance to ischemia constitutive NOS (NOS3) and inducible NOS (NOS2) transcripts levels were determined by Northern analysis. Hypoxia from birth increased NOS3 expression by 238% of normoxic values when normalized to the internal control, alpha-tubulin. NOS2 was not found in normoxic or hypoxic hearts. Release of nitrite, nitrate, and cGMP from hypoxic hearts as well as tissue cGMP was greater than in normoxic hearts. These data indicate that hypoxia from birth in immature hearts elevates expression of constitutive nitric oxice synthase which increases tolerance to ischemia.

未成熟兔子出生的缺氧增加了 与年龄匹配的常氧相比，缺血的孤立心脏的心脏 控件。 我们确定了这种增加的公差是否是由于 内源性一氧化氮产生的改变。 测试 假设，兔子（n = 8/组）从出生中饲养 或7-10天的低氧环境，心脏充满 碳酸氢盐缓冲液。 一氧化氮供体S-硝基谷硫硫代（GSNO） 或一氧化氮合酶抑制剂NG-硝基-L-精氨酸（L-名）为 在全球缺血期30分钟之前增加15分钟，其次是 35分钟再灌注。 GSNO（10 micromole/L）增加了 左心室在常氧心脏中发展为值 与缺氧心脏不同，但对恢复没有影响 在缺氧心脏中发展了压力。 l-name（200 micromole/l） 完全消除了慢性缺氧的心脏保护作用 但对Norm oxix心脏的心脏保护没有影响。 到 确定一氧化氮合酶（NOS）基因表达是否改变 与对缺血本构NOS的耐受性的增加相关 （NOS3）和可诱导的NOS（NOS2）转录本水平由 北方分析。 出生的缺氧增加了NOS3的表达 标准化到内部对照时，差异值的238％， α-微管蛋白。 NOS2在常氧或低氧心脏中没有发现。 从缺氧心脏以及亚硝酸盐，硝酸盐和CGMP释放 组织CGMP大于常氧心脏。 这些数据表明 不成熟心脏中出生的缺氧提升了 构成一氧化氮合酶，可提高耐受性 缺血。