Differential effects of sera from normotensive and hypertensive pregnant women on Ca(2+) metabolism in normal vasular 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 Ca(2+) concentration ([Ca(2+)](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 [Ca(2+)](i) were determined fluorometrically. After a 4-h incubation with serum, basal [Ca(2+)](i) was not significantly altered. However, compared with normal pregnant sera, PE sera markedly reduced hormonally induced Ca(2+) transients. Thus, following acute stimulation of rat VSMC (primary cultures) with 10(-8)M angiotensin II, peak [Ca(2+)](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 [Ca(2+)](i) were qualitatively reproduced in platelets obtained from healthy volunteers. Also, depolarization-activated Ca(2+) influx in VSMC was affected by the different sera groups in a manner similar to that seen with hormonally induced [Ca(2+)](i) responses. The altered [Ca(2+)](i) changes by PE sera disappeared 5 wk after delivery. The effect of the different sera groups on hormonally triggered Ca(2+) transients in normal VSMC, as well as the normalization of [Ca(2+)](i) responses after delivery, suggest the presence of a circulating serum factor in PE. Inasmuch as [Ca(2+)](i) is the major determinant of VSMC tone, it is possible that consequent to the attenuation of [Ca(2+)](i) responses, this putative circulating factor counterbalances the intense vasoconstriction in PE.
Green
Jacob
J
Department of Nephrology, Rambam Medical Center, B. Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Assady
Suheir
S
Department of Nephrology, Rambam Medical Center, B. Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Nakhoul
Farid
F
Department of Nephrology, Rambam Medical Center, B. Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Bick
Tova
T
Department of Nephrology, Rambam Medical Center, B. Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Jakobi
Peter
P
Obstetrics and Gynecology, Rambam Medical Center, B. Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Abassi
Zaid
Z
Department of Physiology and Biophysics, Rambam Medical Center, B. Rappaport Faculty of Medicine, Technion, Haifa, Israel.
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood*; D007425:Intracellular Membranes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D011225:Pre-Eclampsia / Q000097:blood; D011247:Pregnancy / Q000097:blood*; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D000804:Angiotensin II; D002118:Calcium