Differential effects of sera from normotensive and hypertensive pregnant women on Ca²⁺ metabolism in normal vascular smooth muscle cells

The clinical features of preeclampsia have been traditionally ascribed to a generalized vascular endothelial cell dysfunction. The present study investigates the effect of sera from preeclamptic women and normal pregnancy on the metabolism of intracellular Ca²⁺ concentration ([Ca²⁺](i)) in normal cultured vascular smooth muscle cells (VSMC). Sera were obtained from normotensive pregnant women (NTP) (n = 17), preeclamptic women (PE) (n = 15), pregnant women with chronic (essential) hypertension (pregnant EHT) (n = 8), nonpregnant women with essential hypertension (non-pregnant EHT) (n = 12), and age-matched non-pregnant normotensive women (NNP) (n = 18). Serum (10%) was applied to both primary cultures of rat aortic smooth muscle cells and to the A-10 vascular muscle cell line. Levels of [Ca²⁺](i) were determined fluorometrically. After a 4-h incubation with serum, basal [Ca²⁺](i) was not significantly altered. However, compared with normal pregnant sera, PE sera markedly reduced hormonally induced Ca²⁺ transients. Thus, following acute stimulation of rat VSMC (primary cultures) with 10^-8M angiotensin II, peak [Ca²⁺](i) responses (% increment over baseline) were 443 ± 22, 184 ± 18, 259 ± 12, 274 ± 23, and 255 ± 15% in NTP, PE, pregnant EHT, non- pregnant EHT, and NNP, respectively (P < 0.01 PE versus NTP, P < 0.05 PE versus NNP and pregnant and non-pregnant EHT). These effects of sera on [Ca²⁺](i) were qualitatively reproduced in platelets obtained from healthy volunteers. Also, depolarization-activated Ca²⁺ influx in VSMC was affected by the different sera groups in a manner similar to that seen with hormonally induced [Ca²⁺](i) responses. The altered [Ca²⁺](i) changes by PE sera disappeared 5 wk after delivery. The effect of the different sera groups on hormonally triggered Ca²⁺ transients in normal VSMC, as well as the normalization of [Ca²⁺](i) responses after delivery, suggest the presence of a circulating serum factor in PE. Inasmuch as [Ca²⁺](i) is the major determinant of VSMC tone, it is possible that consequent to the attenuation of [Ca²⁺](i) responses, this putative circulating factor counterbalances the intense vasoconstriction in PE.