Cardiovascular effects of prenatal stress-Are there implications for cerebrovascular, cognitive and mental health outcome?

Prenatal stress programs offspring cognitive and mental health outcome. We reviewed whether prenatal stress also programs cardiovascular dysfunction which potentially modulates cerebrovascular, cognitive and mental health disorders. We focused on maternal stress and prenatal glucocorticoid (GC) exposure which have different programming effects. While maternal stress induced cortisol is mostly inactivated by the placenta, synthetic GCs freely cross the placenta and have different receptor-binding characteristics. Maternal stress, particularly anxiety, but not GC exposure, has adverse effects on maternal-fetal circulation throughout pregnancy, probably by co-activation of the maternal sympathetic nervous system, and by raising fetal catecholamines. Both effects may impair neurodevelopment. Experimental data also suggest that severe maternal stress and GC exposure during early and mid-gestation may increase the risk for cardiovascular disorders. Human data are scarce and especially lacking for older age. Programming mechanisms include aberrations in cardiac and kidney development, and functional changes in the renin-angiotensin-aldosterone-system, stress axis and peripheral and coronary vasculature. Adequate experimental or human studies examining the consequences for cerebrovascular, cognitive and mental disorders are unavailable.

Fetal Sheep Mesenteric Resistance Arteries: Functional and Structural Maturation.

BACKGROUND: Fetal blood pressure increases during late gestation; however, the underlying vascular mechanisms are unclear. Knowledge of the maturation of resistance arteries is important to identify the mechanisms and vulnerable periods for the development of vascular dysfunction in adulthood. METHODS: We determined the functional and structural development of fetal sheep mesenteric resistance arteries using wire myography and immunohistochemistry. RESULTS: Media mass and distribution of myosin heavy-chain isoforms showed no changes between 0.7 (100 ± 3 days) and 0.9 (130 ± 3 days) gestation. However, from 0.7 to 0.9 gestation, the resting wall tension increased accompanied by non-receptor-dependent (potassium) and receptor-dependent (noradrenaline; endothelin-1) increases in vasocontraction. Angiotensin II had no contractile effect at both ages. Endothelium-dependent relaxation to acetylcholine and prostaglandin E2 was absent at 0.7 but present at 0.9 gestation. Augmented vascular responsiveness was paralleled by the maturation of sympathetic and sensory vascular innervation. Non-endothelium-dependent relaxation to nitric oxide showed no maturational changes. The expression of vasoregulator receptors/enzymes did not increase between 0.7 and 0.9 gestation. CONCLUSION: Vascular maturation during late ovine gestation involves an increase in resting wall tension and the vasoconstrictor and vasodilator capacity of the mesenteric resistance arteries. Absence of structural changes in the tunica media and the lack of an increase in vasoregulator receptor/enzyme expression suggest that vasoactive responses are due to the maturation of intracellular pathways at this gestational age.