Impaired recovery of intracellular calcium and force after activation in isolated myometrial and subcutaneous resistance arteries from women with preeclampsia.

OBJECTIVES: Preeclampsia is a major cause of maternal and perinatal morbidity and mortality, but its cause is poorly understood. This study investigated whether there is an abnormality of intracellular calcium ([Ca2=]i) and tension during recovery from activation in isolated resistance arteries in preeclampsia and investigated the underlying mechanisms.

METHODS: Subcutaneous and myometrial resistance arteries from preeclamptic, normotensive pregnant and nonpregnant women were mounted on an isometric myograph and loaded with fura-2 to allow simultaneous measurement of force and [Ca2+]i. Arteries were activated by a high-potassium solution or noradrenaline, and the rate of decline in force and [Ca2+]i examined following washout.

RESULTS: Basal tone and [Ca2+]i and rise in force and [Ca2+]i induced by high-potassium solution did not differ between groups but the rate of decline after washout was significantly slowed in both subcutaneous and myometrial arteries from preeclamptic women as compared with normotensive pregnant or nonpregnant women. The rate of decline in force after noradrenaline was also slowed in arteries from preeclamptic women. In subcutaneous resistance arteries from nonpregnant women, removal of the endothelium did not affect the rate of decline in force after high-potassium solution. However, inhibition of the plasma membrane Ca ATPase with carboxyeosin mimicked the findings seen in preeclampsia. In contrast, inhibition of the sarcoplasmic endoreticulum Ca ATPase with cyclopiazonic acid had no effect on the rate of decline in force or [Ca2+]i.

CONCLUSION: The rate of relaxation and decline in [Ca2+]i in resistance arteries are impaired in preeclampsia. This may be mediated by decreased activity of plasma membrane Ca2+ ATPase and could be a mechanism contributing to elevated peripheral resistance and raised blood pressure in preeclampsia.