Effects of vasoactive agents on intracellular calcium and force in myometrial and subcutaneous resistance arteries isolated from preeclamptic, pregnant, and nonpregnant woman

Abstract

Preeclampsia is a common and serious complication of pregnancy, characterized by maternal hypertension and proteinuria, placental insufficiency, and fetal growth restriction. The purpose of this study was to investigate whether intracellular Ca 2+ ([Ca 2+ ] i ) and contractile responses of vascular smooth muscle to vasoactive agents are altered in preeclampsia compared with normal pregnancy and the nonpregnant state. Subcutaneous and myometrial resistance arteries from women who had preeclampsia, normal pregnancy, and nonpregnant women were obtained at the time of cesarean section or hysterectomy. Arteries were mounted on an isometric myograph and loaded with the Ca 2+ indicator, fura-2AM, to permit simultaneous measurement of force and [Ca 2+ ] i . Reponses to endothelium-dependent relaxants (acetylcholine and substance P) and vasoconstrictors (depolarizing potassium solution, phenylephrine, and angiotensin II) were examined. The fall in [Ca 2+ ] i and relaxation in response to acetylcholine was significantly inhibited in both myometrial and subcutaneous arteries from preeclamptic women compared with arteries from nonpregnant or normal pregnant women. However, responses to substance P did not differ between the 3 groups. There were no significant differences in [Ca 2+ ] i or force responses to high potassium, phenylephrine, or angiotensin II in myometrial and subcutaneous resistance vessels in women with preeclampsia compared with normal pregnant women. However, force, but not [Ca 2+ ] i responses to angiotensin II, in subcutaneous vessels from normal pregnant and preeclamptic women were reduced compared with subcutaneous arteries from nonpregnant women, indicating that pregnancy is associated with a reduction in Ca 2+ sensitization in this tissue. A similar effect was not seen in myometrial arteries. Endothelial function is altered in preeclampsia, with loss of effect of acetylcholine, but not substance P. Vasoconstrictor reactivity is not increased in preeclampsia compared with uncomplicated normal pregnancy, and this is unlikely to be an explanation for the increased peripheral vascular resistance seen in preeclampsia.