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Differential Effects of Sera from Normotensive and Hypertensive Pregnant Women on Ca²⁺ Metabolism in Normal Vasular Smooth Muscle Cells

JACOB GREEN^*, SUHEIR ASSADY^*, FARID NAKHOUL^*, TOVA BICK^*, PETER JAKOBI and ZAID ABASSI

^* Department of Nephrology, Rambam Medical Center, B. Rappaport Faculty of Medicine, Technion, Haifa, Israel
Department of Physiology and Biophysics, Rambam Medical Center, B. Rappaport Faculty of Medicine, Technion, Haifa, Israel
Obstetrics and Gynecology, Rambam Medical Center, B. Rappaport Faculty of Medicine, Technion, Haifa, Israel.

Correspondence to Dr. Jacob Green, Department of Nephrology, Rambam Medical Center, Bat-Galim Haifa 31096, Israel. Phone : +972 4 8543251 ; Fax : + 972 4 8542946 ; E-mail greeny{at}rambam.health.gov.il

Abstract. 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), non-pregnant 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.

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673