Figure 7. Diagram of potential mechanisms underlying fetal nicotine exposure-induced hypertensive response in adult offspring.

Perinatal nicotine exposure enhances AT₁R and attenuate AT₂R gene expression through DNA methylation mechanism. Nicotine-mediated enhanced AT₁R/AT₂R ratio predominately heightens Ca²⁺ sensitivity of myofilaments, leading to exaggerated vasoconstriction through both MCL₂₀ phosphorylation-dependent (thick filament) and –independent (thin filament) signaling pathways and development of hypertensive phenotype in adult offspring.