Molecular and Biochemical Mechanisms of Cardiomyopathy Development Following Prenatal Hypoxia—Focus on the NO System

Prenatal hypoxia (PH) disrupts fetal heart development and induces persistent cardiovascular dysfunction in offspring. The nitric oxide (NO) system is pivotal in regulating myocardial function, influencing vascular tone, contractility, and endothelial integrity during development. PH alters NO signaling, leading to endothelial dysfunction, mitochondrial damage, and oxidative stress, which exacerbate myocardial impairment and increase cardiomyocyte apoptosis. Elevated nitrosative stress, through excessive reactive nitrogen species, further exacerbates these effects, promoting inflammation and cellular injury. The interaction between NO and hypoxia-inducible factor (HIF) also mediates adaptive responses to PH. Additionally, NO modulates the expression of heat shock protein 70 (HSP70), providing cellular protection under stress. This review highlights the role of NO in PH-induced cardiovascular damage and evaluates the therapeutic potential of NO modulators—Angiolin, Tiotriazoline, Mildronate, and L-arginine—as promising agents for cardioprotection. These compounds mitigate oxidative stress, improve endothelial function, and counteract the adverse effects of PH on the heart, suggesting novel therapeutic strategies for preventing cardiovascular dysfunction in offspring exposed to prenatal hypoxia.