Table 1.
Renal programming related to aberrant renin-angiotensin-aldosterone system (RAAS) in animal models. Studies tabulated according to animal models, species, and age at evaluation. CKD, chronic kidney disease; L-NAME, L-NG-Nitro arginine methyl ester; LPS, lipopolysaccharide; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; PDTC, pyrrolidine dithiocarbamate; DEX, dexamethasone; Cr, creatinine; SD, Sprague Dawley; SHR, spontaneously hypertensive rat; M, male; F, female; BP, blood pressure; GFR, glomerular filtration rate; ↑, increased; ↓, decreased; ↔, unaltered; PRR, (pro)renin receptor; PRA, plasma renin activity; ACE, angiotensin-converting enzyme; ACE2, angiotensin-converting enzyme 2; AGT, angiotensinogen; AT1R, angiotensin type 1 receptor; AT2R, angiotensin type 2 receptor.
| Animal Models | Intervention Period | Species/Gender | Age at Evaluation | Renal Phenotype | Alterations of the RAAS | Ref. |
|---|---|---|---|---|---|---|
| 20% w/v sucrose in drinking water | Pregnancy | SD rat/M | 90 weeks | ↑BP | ↑AT1R mRNA and protein | [51] |
| High-fructose diet, 60% | Pregnancy and Lactation | SD rat/M | 12 weeks | ↑BP | ↓AT2R mRNA | [52] |
| High-fructose diet, 60% | Pregnancy and Lactation | SD rat/M | 12 weeks | ↑BP, altered renal transcriptome | ↑Renin mRNA | [53] |
| Protein restriction, 9% | Pregnancy | SD rat/M | 4 weeks | ↑BP, ↔GFR | ↑AT1R protein and ↓AT2R protein, ↔ANG level | [54,55] |
| Protein restriction, 6% | Pregnancy | SD rat/M and F | 4 weeks | ↑BP | ↓AT1R and AT2R protein at birth; ↑AT1R and AT2R protein at 4 wk | [56] |
| Protein restriction, 6% | Pregnancy | SD rat/M and F | 8 weeks | ↑BP, ↓nephron number | ↓PRA, ↓AT1R mRNA and protein, ↑Aldosterone | [57] |
| Protein restriction, 8% | Lactation | Wistar rat/M | 150 days | ↑BP, ↑GFR, ↑Proteinuria | ↑AT1R protein and↓AT2R protein | [58] |
| Protein restriction, 8.5% | Pregnancy | SD rat/M | 22 weeks | ↑BP, ↔GFR | ↓renin mRNA and protein; and ↓renal ANG II level at 1–5 days of age | [59,60] |
| Protein restriction, 9% | 1 week before conception and throughout pregnancy | FVB/NJ mouse/F | 24 weeks | ↑BP | ↓ACE2 protein | [61] |
| Protein restriction | Second half of pregnancy | SD and Wistar rat/M and F | 11 months | ↑BP | ↑PRA, ↑AT1R mRNA and protein | [62,63] |
| 50% caloric restriction | Day 28 to day 78 of gestation | Sheep/M and F | 9 months | ↑BP | ↑ACE protein | [64] |
| High-fat diet, 58% | Pregnancy and Lactation | SD rat/M | 16 weeks | ↑BP | ↑AGT and ACE mRNA, and↑AT1R protein | [65] |
| High-fat diet, 58% | 5 weeks before the delivery and throughout pregnancy and lactation | SD rat/M and F | 6 months | ↔BP, ↓GFR, ↑glomerular injury, ↑tubulointerstitial injury, altered renal transcriptome | ↑ACE and AT1R mRNA in F | [66] |
| High-salt diet, 8% | Pregnancy | Wistar rat/F | 12 weeks | ↑BP | ↑ANG II | [67] |
| 0.03% low-salt diet | Last 7 days of pregnancy | SD rat/M and F | 12 weeks | ↑BP | ↑PRA | [68] |
| Maternal renovascular hypertension | Pregnancy | SD rat/M | 16 weeks | ↑BP | ↑AT1R protein | [69] |
| Maternal renovascular hypertension | Pregnancy | Rabbit/F | 30 weeks | ↑BP | ↓PRA at 10 week | [70] |
| Maternal adenine-induced CKD | Pregnancy and lactation | SD rat/M | 12 weeks | ↑BP, renal hypertrophy | ↓AT2R and MAS receptor mRNA | [71] |
| Maternal streptozotocin-induced diabetes | Pregnancy | C57BL/6 mouse/M | 20 weeks | ↑BP, microalbuminuria | ↑AT1R and ACE mRNA, ↓ACE2 mRNA | [72] |
| Maternal streptozotocin-induced diabetes | Pregnancy | Wistar rat/M | 2 months | ↑BP | ↑ACE activity | [73] |
| Continuous light exposure | Pregnancy and lactation | SD rat/M | 12 weeks | ↑BP | ↑Renin, PRR, AGT, ACE, ACE2, and AT1R mRNA |
[74] |
| Maternal L-NAME exposure | Pregnancy | SD rat/M | 12 weeks | ↑BP | ↑Renin and ACE mRNA | [75] |
| Maternal LPS exposure | Pregnancy | SD rat/M and F | 24 weeks | ↑BP, ↓nephron number and GFR | ↑ACE mRNA | [76] |
| Placenta insufficiency | Pregnancy | SD rat/M | 16 weeks | ↑BP | ↓Renin and AGT mRNA at birth, ↑Renin and AGT mRNA, ↑ACE activity at 16 week | [77] |
| Prenatal hypoxia | From embryonic day 14.5 until birth | CD1 mouse/M and F | 12 months | Microalbuminuria, glomerular hypertrophy and renal fibrosis, ↓nephron number | ↑Renin and AT1R mRNA | [78] |
| Maternal nicotine exposure | Pregnancy | SHR/M | 9 weeks | ↑BP, ↓Glomerular mass | ↑AT1R mRNA | [79] |
| Maternal nicotine exposure | Pregnancy | SD rat/M | 5 months | ↑BP | ↑AT1R protein, ↓AT2R protein | [80] |
| Maternal caffeine exposure | Pregnancy | C57BL/6 mouse/M | 3 months | ↑BP | ↑Renin and AT1R mRNA | [81] |
| Maternal TCDD and dexamethasone exposure | Pregnancy and Lactation | SD rat/M | 16 weeks | ↑BP | ↑ACE mRNA | [82] |
| Neonatal PDTC administration | Lactation | Munich-Wistar rat/M | 10 months | ↑BP | ↑Renin and AGT mRNA at 3 month; ↓Renin and AGT at 10 month | [83] |
| Prenstal DEX exposure | Pregnancy | SD rat/M | 16 weeks | ↑BP | ↑AGT and AT1R mRNA | [84] |
| Prenstal DEX exposure | Pregnancy | SD rat/M | 16 weeks | ↑BP | ↑Renin and PRR mRNA | [85] |
| Prenatal DEX plus post-weaning high-fat diet | Pregnancy | SD rat/M | 16 weeks | ↑BP | ↑Renin and ACE mRNA | [86] |
| Neonatal DEX administration | Day 1 to day 3 after birth | SD rat/M | 16 weeks | ↑BP | ↓AGT, ACE, and ACE2 mRNA | [87] |
| Prenatal betamethasone exposure | 2 doses, 24 h apart at gestational day 80 | Sheep/M | 1.8 years | ↑BP | ↑ACE activity, ↓ACE2 activity | [88] |