Modulation of iNOS activity in age-related cardiac dysfunction.
Modulation of iNOS activity in age-related cardiac dysfunction.
复制标题
年龄相关性心脏功能障碍中 iNOS 活性的调节。
DOI：
10.1016/j.lfs.2003.09.076
复制
发表时间：
2004
期刊：
影响因子：
6.1
通讯作者：
Watson,RonaldR
中科院分区：
文献类型：
--
作者：
Yang,Bo;Larson,DouglasF;Watson,RonaldR
基于诱导型一氧化氮合酶（iNOS）在心力衰竭中的作用，我们假设与年轻小鼠相比，心肌中iNOS的表达升高有助于与年龄相关的左心室（LV）功能下降。在年老的野生型（WT）雄性小鼠（16个月）中，而在年轻的WT雄性小鼠（6个月）中，心脏iNOS mRNA和蛋白表达被单独鉴定。通过体内压力-容积环分析，在老年WT小鼠中发现了与年龄相关的LV功能障碍。特异性iNOS抑制剂氨基胍（AMG，10 mg/Kg，i. v.或输注，n = 15）和S-甲基异噻唑啉（MITU，3 mg/Kg，i. v. n = 7）可使老年小鼠的LV功能障碍改善为年轻小鼠的LV功能障碍，而L-精氨酸（10 mg/Kg，i. v. n = 7）可使老年小鼠的LV功能障碍下降。所有三种药物对年轻WT小鼠或年老iNOS敲除（KO）小鼠的LV功能均无影响。NOx和cGMP水平仅在老龄WT小鼠（n = 6）中显著较高，而cGMP水平在AMG给药后降至正常。总之，这些结果表明，iNOS/NO/cGMP途径可能有助于在衰老过程中的心室功能障碍，抑制iNOS活性显着改善老年小鼠的心功能。
Based on the role of inducible nitric oxide synthase (iNOS) in heart failure, we hypothesized that the elevated expression of iNOS compared to young mice in the myocardium contributes to the age-related decline of left ventricular (LV) function. Cardiac iNOS mRNA and protein expression was singularly identified in old, wild type (WT) male mice (I6-month) and not in young WT male mice (6-month). Characterized with in vivo pressure-volume loops analysis, an age-related LV dysfunction was found in the old WT mice. The LV dysfunction of the aged mice was modified to that of the younger mice by the specific iNOS inhibitors, aminoguanidine (AMG, 10 mg/Kg, i.v. or infusion, n = 15) and S-methyl-isothiourea (MITU, 3 mg/Kg, i.v. n = 7), and declined with L-arginine (10 mg/Kg, i.v. n = 7). All three drugs had no effects on the LV function of young WT mice or old iNOS knockout (KO) mice. The NOxand cGMP levels were significantly higher only in the old WT mice (n = 6) and cGMP levels decreased to normal with AMG administration. In conclusion, these results suggested that the iNOS/NO/cGMP pathway may contribute to ventricular dysfunction during the aging process and that inhibition of iNOS activity significantly improved heart function in aged mice.