Accelerated age-related decline in renal and vascular function in female rats following early-life growth restriction

被引:20
|
作者
Black, M. Jane [1 ,2 ]
Lim, Kyungjoon [1 ,2 ]
Zimanyi, Monika A. [1 ,2 ]
Sampson, Amanda K. [3 ]
Bubb, Kristen J. [3 ]
Flower, Rebecca L. [3 ]
Parkington, Helena C. [3 ]
Tare, Marianne [3 ]
Denton, Kate M. [3 ]
机构
[1] Monash Univ, Dept Anat, Clayton, Vic 3800, Australia
[2] Monash Univ, Dev Biol, Clayton, Vic 3800, Australia
[3] Monash Univ, Dept Physiol, Clayton, Vic 3800, Australia
基金
英国医学研究理事会;
关键词
aging; arterial pressure; fetal programming; kidney; sex differences; CONVERTING-ENZYME-INHIBITION; ANGIOTENSIN TYPE-2 RECEPTOR; LOW-BIRTH-WEIGHT; CATCH-UP GROWTH; INTRAUTERINE GROWTH; NITRIC-OXIDE; SEX-DIFFERENCES; AGING KIDNEY; CARDIOVASCULAR-DISEASE; DEVELOPMENTAL ORIGINS;
D O I
10.1152/ajpregu.00403.2014
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Many studies report sexual dimorphism in the fetal programming of adult disease. We hypothesized that there would be differences in the age-related decline in renal function between male and female intrauterine growth-restricted rats. Early-life growth restriction was induced in rat offspring by administering a low-protein diet (LPD; 8.7% casein) to dams during pregnancy and lactation. Control dams were fed a normal-protein diet (NPD; 20% casein). Mean arterial pressure (MAP) and renal structure and function were assessed in 32- and 100-wk-old offspring. Mesenteric artery function was examined at 100 wk using myography. At 3 days of age, body weight was similar to 24% lower (P < 0.0001) in LPD offspring; this difference was still apparent at 32 wk but not at 100 wk of age. MAP was not different between the male NPD and LPD groups at either age. However, MAP was greater in LPD females compared with NPD females at 100 wk of age (similar to 10 mmHg; P < 0.001). Glomerular filtration rate declined with age in the NPD male, LPD male and LPD female offspring (similar to 45%, all P < 0.05), but not in NPD female offspring. Mesenteric arteries in the aged LPD females had reduced sensitivity to nitric oxide donors compared with their NPD counterparts, suggesting that vascular dysfunction may contribute to the increased risk of disease in aged females. In conclusion, females growth-restricted in early life were no longer protected from an age-related decline in renal and arterial function, and this was associated with increased arterial pressure without evidence of renal structural damage.
引用
收藏
页码:R1153 / R1161
页数:9
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