Proposed mechanisms for developmental programming of BP
| Programmed Characteristic | Proposed Mechanism/Evidence Affecting BP in Programmed Offspring versus Control Subjects | Reference |
|---|---|---|
| Reduced nephron number | Reduced filtration surface area | 10,18,41,43 |
| Renal dysfunction | ||
| Increased renal vascular reactivity | ↑renal artery response to β-adrenergic stimuli and sensitivity to adenylyl cyclase in growth-restricted rats | 184,186,187 |
| Altered vascular reactivity | ↓flow-mediated dilation in LBW children | 107,188–190 |
| ↑uric acid | ||
| Endothelial dysfunction | ||
| Impaired vascular structure and capillary density | ||
| Altered RAS | Administration of inhibitors of RAS abrogates later hypertension | 4,30,111,177,191 |
| Administration of angiotensin II causes increased hypertensive response | ||
| Evidence of expression of AT1R and AT2R and ACE activity are divergent at different stages and in different models of programming | ||
| Overall, programmed suppression of intrarenal RAS during nephrogenesis and postnatal upregulation of AT1R are most consistent | ||
| Altered sodium handling | ↓fractional excretion of sodium | 22,109,110,174,192 |
| ↑expression of BSC1 and TSC | ||
| ↑expression of glucocorticoid receptor | ||
| ↑expression of glucocorticoid responsive α1 and β1 subunits of Na/K-ATPase | ||
| ↑expression of NHE3 | ||
| ↑expression of β and γ ENaC | ||
| Increased sympathetic nervous system activity | Renal denervation reduced systolic BP and sodium transporter expression | 193 |
| Catch-up growth/obesity | Higher BP in children who catch up fastest | 98,154 |
| Reduced flow-mediated dilation with higher rate of weight gain |
AT1R, angiotensin subtype 1 receptor; AT2R, angiotensin subtype 2 receptor; BSC1, bumetanide-sensitive co-transporter; ENaC, epithelial sodium channel; NHE3, sodium hydrogen exchanger; RAS, renin-angiotensin system; TSC, thiazide-sensitive co-transporter.