| First Author | Li W | Year | 2004 |
| Journal | J Mol Cell Cardiol | Volume | 37 |
| Issue | 3 | Pages | 671-80 |
| PubMed ID | 15350840 | Mgi Jnum | J:102136 |
| Mgi Id | MGI:3606846 | Doi | 10.1016/j.yjmcc.2004.05.005 |
| Citation | Li W, et al. (2004) Premature death and age-related cardiac dysfunction in male eNOS-knockout mice. J Mol Cell Cardiol 37(3):671-80 |
| abstractText | The aims of our study were to determine mortality, and age- and genotype-related cardiac phenotype in endothelial nitric oxide synthase (NOS) knockout (-/-) and wild-type (+/+) mice. Male and female (-/-) and male and female (+/+) conscious mice were studied at different ages by echocardiography and tail-cuff blood pressure (BP) measurement. Only 50% male (-/-) mice lived longer than 21 months whereas 89% (+/+) mice were still alive after 24 months (P < 0.005). There was little mortality in female mice of either genotype. Both (-/-) and (+/+) male mice have normal cardiac dimensions and function at 5.5 months. However, (-/-) mice developed cardiac dilation and dysfunction at 21 months as evidenced by a significant increase (P < 0.05) in left ventricular (LV) end-diastolic diameter from 2.69 +/- 0.13 to 3.13 +/- 0.09 mm, LV end-systolic diameter from 1.28 +/- 0.11 to 1.86 +/- 0.12 mm, LV end-diastolic cavity volume from 21 +/- 2.8 to 31 +/- 2.5 microl and LV mass from 19 +/- 2.5 to 27 +/- 1.9 mg/10 g and a significant decrease (P < 0.05) in ejection fraction (from 65 +/- 3.3% to 41 +/- 4.6%), shortening fraction (from 53 +/- 2.2% to 41 +/- 3.4%), LV posterior wall thickening (from 27 +/- 2% to 12 +/- 4%) and septum thickening (from 27 +/- 2% to 12 +/- 4%) compared with those at 5.5 months. There was a clear increase in cardiac weight and cardiac dilation by hematoxylin and eosin in male (-/-) mice at 21 months. BP in male (-/-) mice fell with the cardiac dysfunction, whereas female (-/-) mice were hypertensive even at 21 months. The level of mRNA for neuronal NOS and inducible NOS was greater in all females compared to males. These results indicate that male (-/-) mice have a significantly shorter lifespan than (+/+) or female mice, and male (-/-) mice develop cardiac dysfunction with age. |
