Table 1.
Reprogramming strategies targeting the NO pathway to prevent hypertension and kidney disease of developmental programming in animal models.
| Interventions | Animal Models | Intervention Period | Species/Gender | Age at Measure (Week) | Protective Effects | Reference |
|---|---|---|---|---|---|---|
| Substrate for NOS | ||||||
| l-arginine | Maternal streptozotocin-induced diabetes | 3 weeks to 24 weeks | Wistar/M | 24 | Prevented hypertension and glomerular hypertrophy | [84] |
| l-arginine + antioxidants | Genetic hypertension | 2 weeks before until 8 weeks after birth | SHR/Mand F | 9 | Prevented hypertension | [85] |
| l-arginine + antioxidants | Genetic hypertension | 2 weeks before until 4 weeks after birth | FHH/M and F | 36 | Prevented hypertension, proteinuria, and glomerulosclerosis | [86] |
| l-arginine + antioxidants | Genetic hypertension | 2 weeks before until 8 weeks after birth | SHR/M and F | 50 | Prevented hypertension and proteinuria | [87] |
| l-citrulline | Maternal 50% caloric restriction | 3 weeks before until 3 weeks after birth | SD/M | 12 | Prevented kidney damage, increased nephron number | [88] |
| l-citrulline | Maternal nitric oxide deficiency | 3 weeks before until 3 weeks after birth | SD/M | 12 | Prevented hypertension | [46] |
| l-citrulline | Maternal streptozotocin-induced diabetes | 3 weeks before until 3 weeks after birth | SD/M | 12 | Prevented hypertension and kidney damage, increased nephron number | [38] |
| l-citrulline | Prenatal dexamethasone exposure | 3 weeks before until 3 weeks after birth | SD/M | 12 | Prevented hypertension, increased nephron number | [41] |
| l-citrulline | Genetic hypertension | 4 weeks to 12 weeks | SHR/M | 12 | Prevented hypertension | [89] |
| l-citrulline | Genetic hypertension | 2 weeks before until 6 weeks after birth | SHR/M and F | 50 | Prevented hypertension | [90] |
| Asymmetric dimethylarginine (ADMA)-lowering agents | ||||||
| Resveratrol | Prenatal dexamethasone plus TCDD exposure | 3 weeks before until 3 weeks after birth | SD/M | 12 | Prevented hypertension | [91] |
| Melatonin | Maternal high-fructose diet plus post-weaning high-salt diet | 3 weeks before until 3 weeks after birth | SD/M | 12 | Prevented hypertension | [92] |
| Aliskiren | Maternal caloric restriction | 2 weeks to 4 weeks | SD/M | 12 | Prevented hypertension | [60] |
| N-acetylcysteine | Prenatal dexamethasone plus postnatal high-fat diet | 3 weeks before until 3 weeks after birth | SD/M | 16 | Prevented hypertension | [93] |
| Dimethyl fumarate | Prenatal dexamethasone plus postnatal high-fat diet | 3 weeks to 6 weeks | SD/M | 16 | Prevented hypertension | [94] |
| Metformin | Genetic hypertension | 4 weeks to 12 weeks | SHR/M | 12 | Prevented hypertension | [95] |
| N-acetylcysteine | Genetic hypertension | 4 weeks to 12 weeks | SHR/M | 12 | Prevented hypertension | [96] |
| Melatoin | Genetic hypertension | 4 weeks to 12 weeks | SHR/M | 12 | Prevented hypertension | [97] |
| Aliskiren | Genetic hypertension | 4 weeks to 12 weeks | SHR/M | 12 | Prevented hypertension | [61] |
| NO donor | ||||||
| Nitrate | Genetic hypertension | 4 weeks to 12 weeks | SHR/M | 12 | Prevented hypertension | [89] |
| Molsidomine | Genetic hypertension | 2 weeks before until 4 weeks after birth | FHH/M and F | 42 | Prevented hypertension | [98] |
| Pentaerythritol tetranitrate | Genetic hypertension | 3 weeks before until 3 weeks after birth | SHR/M and F | 24 | Prevented hypertension | [99] |
| Others | ||||||
| Short interfering RNA targeting PIN | Genetic hypertension | 4 weeks to 12 weeks | SHR/M | 12 | Prevented hypertension | [100] |
| Melinjo (Gnetum gnemon) Seed Extract | Maternal high-fructose diet | Birth to 3 weeks | Wistar/F | 17 | Prevented hypertension | [101] |
Studies tabulated according to types of intervention, animal models and age at measure. TCDD = 2,3,7,8-tetrachlorodibenzo-p-dioxin. SD = Sprague–Dawley rat. SHR = spontaneously hypertensive rat. FHH = Fawn-hooded hypertensive rat. M = male. F = female. PIN = protein inhibitor of neuronal nitric oxide synthase.