Reckelhoff J F, Kellum J A, Blanchard E J, Bacon E E, Wesley A J, Kruckeberg W C
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216.
Life Sci. 1994;55(24):1895-902. doi: 10.1016/0024-3205(94)00521-4.
The present study was performed to test the hypothesis that excretion of nitric oxide metabolites, nitrate and nitrite, are decreased with progressive aging in rats and that a decrease in nitric oxide precursor, L-arginine, also decreases with aging. Urinary nitrate/nitrite excretory rates and serum L-arginine levels were measured in male Sprague Dawley rats, ranging in ages from 3 to 25 months. Proteinuria increased dramatically with aging. Conversely, urinary nitrate/nitrite excretion decreased by 50% and 80% in rats, aged 12 months and 17 months, respectively. There was no further decrease in urinary nitrate/nitrite excretion in very old rats, aged 23-24 months. Glomerular filtration rate (GFR) was also measured in some of the rats, aged 3-5 mos and 17 mos. GFR was not different between old and young rats, suggesting that a decrease in GFR could not account for the decrease in urinary nitrate/nitrite excretion in the old rats. However, serum L-arginine levels were decreased with aging, by 30% and 50% in rats, aged 13-15 months and 24-25 months, respectively, when compared with young rats. These data confirm our hypothesis and suggest that nitric oxide (NO) production may decrease with aging and that one mechanism by which nitric oxide production could be decreased with age is a lack of the endogenous substrate, L-arginine. Because NO has been implicated to be involved in many physiological processes, age-related decreases in NO production could have far-reaching adverse effects in the aging individual.
随着大鼠年龄的增长，一氧化氮代谢产物硝酸盐和亚硝酸盐的排泄量会减少，且一氧化氮前体L-精氨酸的含量也会随衰老而降低。对年龄在3至25个月的雄性斯普拉格-道利大鼠测量了尿硝酸盐/亚硝酸盐排泄率和血清L-精氨酸水平。蛋白尿随年龄增长显著增加。相反，12个月龄和17个月龄大鼠的尿硝酸盐/亚硝酸盐排泄量分别减少了50%和80%。在23至24个月龄的老龄大鼠中，尿硝酸盐/亚硝酸盐排泄量没有进一步下降。还对部分3至5个月龄和17个月龄的大鼠测量了肾小球滤过率（GFR）。老龄和年轻大鼠的GFR没有差异，这表明GFR的降低并不能解释老龄大鼠尿硝酸盐/亚硝酸盐排泄量的减少。然而，与年轻大鼠相比，血清L-精氨酸水平随年龄增长而降低，13至15个月龄和24至25个月龄大鼠的血清L-精氨酸水平分别降低了30%和50%。这些数据证实了我们的假设，并表明一氧化氮（NO）的产生可能随衰老而减少，且随着年龄增长一氧化氮产生减少的一种机制可能是内源性底物L-精氨酸的缺乏。由于NO已被认为参与许多生理过程，与年龄相关的NO产生减少可能会对衰老个体产生深远的不利影响。
