Impacts of Exogenously Derived Nitrogen Oxide and Sulfur Compounds on the Structure and Function of the Vascular Endothelium Link Pregnancy Hypertension with Later Life Hypertension

The relationship between pregnancy hypertension and later life hypertension is explained by long-term impacts of environmental oxidants on the vascular endothelium. These impacts may precede the onset of the disease as a primary defect and may participate in the pathogenesis of hypertension itself. Continuous exposure to strong exogenous oxidants such as NOx (NO and NO2) reversibly oxidizes oxyhemoglobin (Fe2+) to methemoglobin (Fe3+), and irreversible methemoglobinemia can arise because of disruption of the oxidant/antioxidant balance supported by SO2 metabolites, as inhibitors of antioxidants, and by synergistic degradation of antioxidant thiols. Methemoglobin by itself and from heme, redox-active ferric iron as product of methemoglobin catabolism, have prooxidant properties and cause important structural and functional changes in the vascular endothelium such as growth arrest, senescence, morphological alterations and cell apoptosis. In 1975, an epidemiological study among 204 pregnant women in Labin (Croatia) identified 30 (14.7%) cases of preeclampsia and 25 (12.3%) cases of hypertension in pregnancy. Ten years later, we found a significant number of hypertension cases (N=5; P=0.0027), and among them, we found a significant number of pregnancy-induced hypertension cases (N=3; P=0.0003) and a significant number of psychoneurotic disturbances (P=0.0190), but these conditions were not found in the normotensive women ten years after giving birth (P = 0.1161). Our original findings confirm that hypertension in pregnancy is not a transient impairment but instead is an extension of the effects of exogenously induced oxidative stress on the structure and function of the vascular endothelial, and indicate delayed effects plausibly manifesting as hypertension in later life.