Table 4.

Proposed mechanisms for developmental programming of BP

Programmed CharacteristicProposed Mechanism/Evidence Affecting BP in Programmed Offspring versus Control SubjectsReference
Reduced nephron numberReduced filtration surface area10,18,41,43
Renal dysfunction
Increased renal vascular reactivity↑renal artery response to β-adrenergic stimuli and sensitivity to adenylyl cyclase in growth-restricted rats184,186,187
Altered vascular reactivity↓flow-mediated dilation in LBW children107,188–190
↑uric acid
Endothelial dysfunction
Impaired vascular structure and capillary density
Altered RASAdministration of inhibitors of RAS abrogates later hypertension4,30,111,177,191
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 sodium22,109,110,174,192
↑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 activityRenal denervation reduced systolic BP and sodium transporter expression193
Catch-up growth/obesityHigher BP in children who catch up fastest98,154
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.