Vinturache Angela E, Smith Francine G
Department of Physiology & Pharmacology; Alberta Children's Hospital Research Institute for Child and Maternal Health, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive, NW, Calgary, AB, T2N 4N1, Canada.
BMC Physiol. 2016 Apr 18;16:3. doi: 10.1186/s12899-016-0022-3.
Evidence suggests a critical role for the renin-angiotensin system in regulating renal function during postnatal development. However, the physiological relevance of a highly elevated renin-angiotensin system early in life is not well understood, nor which angiotensin receptors might be involved. This study was designed to investigate the roles of angiotensin receptors type 1 (AT1R) and type 2 (AT2R) in regulating glomerular and tubular function during postnatal development.
The renal effects of the selective antagonist to AT1R, ZD 7155 and to AT2R, PD 1233319 were evaluated in two groups of conscious chronically instrumented lambs aged ~ one week (N = 8) and ~ six weeks (N = 10). Two experiments were carried out in each animal and consisted of the assessment of renal variables including glomerular and tubular function, for 30 min before (Control) and 60 min after infusion of ZD 7155 and PD 123319, respectively. Statistical significance was determined using parametric testing (Student t-test, analysis of variance ANOVA) as appropriate.
ZD 7155 infusion was associated with a significant decrease in glomerular filtration rate and filtration fraction at one but not six weeks; urinary flow rate decreased significantly in older animals, whereas sodium excretion and free water clearance were not altered. There was an age-dependent effect on potassium handling along the nephron, potassium excretion decreasing after ZD 7155 infusion in younger but not in older lambs. PD 123319 had no significant effects on glomerular filtration rate and tubular function in either age group.
These results provide evidence to support an important role for AT1Rs in mediating the renal effects of angiotensin II during postnatal maturation in conscious developing animals. In contrast to a role for AT2Rs later in life, there appears to be no role for AT2Rs in influencing the renal effects of Angiotensin II in the postnatal period.
有证据表明肾素 - 血管紧张素系统在出生后发育过程中调节肾功能方面起着关键作用。然而，生命早期肾素 - 血管紧张素系统高度升高的生理相关性尚未得到充分理解，也不清楚哪些血管紧张素受体可能参与其中。本研究旨在探讨1型血管紧张素受体（AT1R）和2型血管紧张素受体（AT2R）在出生后发育过程中调节肾小球和肾小管功能的作用。
在两组有意识的、长期植入仪器的羔羊中评估了AT1R选择性拮抗剂ZD 7155和AT2R选择性拮抗剂PD 123319的肾脏效应，一组年龄约为1周（N = 8），另一组年龄约为6周（N = 10）。对每只动物进行了两项实验，包括在分别输注ZD 7155和PD 123319之前30分钟（对照）和之后60分钟评估包括肾小球和肾小管功能在内的肾脏变量。根据情况使用参数检验（学生t检验、方差分析ANOVA）确定统计学显著性。
输注ZD 7155后，1周龄而非6周龄羔羊的肾小球滤过率和滤过分数显著降低；老年动物的尿流率显著降低，而钠排泄和自由水清除率未改变。沿肾单位对钾的处理存在年龄依赖性效应，ZD 7155输注后年轻羔羊的钾排泄减少，而老年羔羊则未减少。PD 123319对两个年龄组的肾小球滤过率和肾小管功能均无显著影响。
这些结果提供了证据，支持AT1R在有意识的发育中动物出生后成熟过程中介导血管紧张素II的肾脏效应方面发挥重要作用。与生命后期AT2R的作用相反，AT2R在出生后时期似乎对血管紧张素II的肾脏效应没有影响。
