Abstract
Intracellular free calcium [Ca2+]i and magnesium [Mg2+]i ions play major roles in the mechanism of vascular smooth muscle (VSM) contraction. Although essential hypertension and abnormal intracellular homeostasis of these ions have long been recognized as major icons in the pathogenesis of pre-eclampsia, the underlying mechanism(s) remain poorly understood.
Alterations of vascular smooth muscle and platelet intracellular cations [Ca2+]i, [Mg2+]i and [H+]i relative to plasma concentrations of these ions in nitric oxide synthase (NOS) blockade-induced models of pre-eclampsia have been evaluated in the present study.
Pregnant rats injected with the NOS inhibitor, NG-nitro-l-arginine methyl ester (L-NAME) developed a significantly elevated arterial blood pressure, proteinuria and other clinical parameters characteristic of pre-eclampsia compared to age-matched pregnant and non-pregnant rat controls that received the L-NAME vehicle only. Plasma total calcium concentration was significantly lower in pre-eclamptic rat models compared to normal pregnant rats (10.29±0.08 vs 10.67±0.18 mg/dl, p<0.05). A significant increase in plasma calcium was observed in pregnant controls compared to non-pregnant rats (10.67±0.18 vs 10.14±0.09 mg/dl, p<0.01). Plasma Ca2+ levels in pre-eclamptic rats were consistently lower than those of pregnant controls (5.69±0.09 vs 5.98±0.06 mg/dl, p<0.05). Resting levels of [Ca2+]i was significantly higher in pre-eclamptic rats than in pregnant controls. (351±45.2 vs 196±23.2 nmol/l, p<0.01). Blood pH was significantly increased in pre-eclamptic rats as compared to pregnant controls (7.16±0.02 vs 7.05±0.03, p<0.05). There was no significant difference in plasma and intracellular magnesium concentrations between the three rat groups.
These findings suggest that a significantly decreased plasma level of Ca2+ coupled with a concomitant increase in VSM [Ca2+]i concentrations and an altered blood pH are associated with pre-eclampsia in the pregnant rat. Routine monitoring of serum pH, Ca2+ and Mg2+ especially in the late third trimester, may have potential in the early detection of patients at risk for pre-eclampsia, and monitoring the progress of diverse therapeutic regimens during clinical management.