Large Conductance Ca2+-Activated K+ Channels Modulate Uterine α1-Adrenergic Sensitivity in Ovine Pregnancy

Oxidative Medicine and Cellular Longevity

2019

During pregnancy, the adaptive changes in uterine circulation and the formation of the placenta are essential for the growth of the fetus and the well-being of the mother. The steroid hormone estrogen plays a pivotal role in this adaptive process. An insufficient blood supply to the placenta due to uteroplacental dysfunction has been associated with pregnancy complications including preeclampsia and intrauterine fetal growth restriction (IUGR). Oxidative stress is caused by an imbalance between free radical formation and antioxidant defense. Pregnancy itself presents a mild oxidative stress, which is exaggerated in pregnancy complications. Increasing evidence indicates that oxidative stress plays an important role in the maladaptation of uteroplacental circulation partly by impairing estrogen signaling pathways. This review is aimed at providing both an overview of our current understanding of regulation of the estrogen-NOS-NO-KCa pathway by reactive oxygen species (ROS) in uteroplacental tissues and a link between oxidative stress and uteroplacental dysfunction in pregnancy complications. A better understanding of the mechanisms will facilitate the development of novel and effective therapeutic interventions.

Section: E2β Signaling and Uteroplacental Circulation In Physiologmentioning

confidence: 99%

Effect of Oxidative Stress on the Estrogen-NOS-NO-K_Ca Channel Pathway in Uteroplacental Dysfunction: Its Implication in Pregnancy Complications

Song

Oxidative Medicine and Cellular Longevity

2019

“…Phenylephrine-induced contraction of ovine uterine arteries is potentiated by the BK Ca channel inhibitor tetraethylammonium [210]. Similarly, phenylephrine infusion-induced increase in uterine vascular resistance in pregnant sheep is enhanced by tetraethylammonium [218]. Pregnancy increases AT 2 receptor expression in the endothelium of uterine arteries in pregnant rats, which is associated with blunted uterine vasoconstriction to angiotensin II [202].…”

Section: Ca 2+ Spark/stoc Couplingmentioning

confidence: 99%

Uteroplacental Circulation in Normal Pregnancy and Preeclampsia: Functional Adaptation and Maladaptation

2021

IJMS

Uteroplacental blood flow increases as pregnancy advances. Adequate supply of nutrients and oxygen carried by uteroplacental blood flow is essential for the well-being of the mother and growth/development of the fetus. The uteroplacental hemodynamic change is accomplished primarily through uterine vascular adaptation, involving hormonal regulation of myogenic tone, vasoreactivity, release of vasoactive factors and others, in addition to the remodeling of spiral arteries. In preeclampsia, hormonal and angiogenic imbalance, proinflammatory cytokines and autoantibodies cause dysfunction of both endothelium and vascular smooth muscle cells of the uteroplacental vasculature. Consequently, the vascular dysfunction leads to increased vascular resistance and reduced blood flow in the uteroplacental circulation. In this article, the (mal)adaptation of uteroplacental vascular function in normal pregnancy and preeclampsia and underlying mechanisms are reviewed.

“…On the other hand, the production of vasodilators such as NO, calcitonin gene-related peptide, and adrenomedullin is increased in pregnancy and they produce vasorelaxation of uterine arteries apparently via cGMP-mediated activation of the BK Ca channel [ 231 , 266 , 267 ]. Inhibition of the BK Ca channel enhances uterine vasoconstriction induced by α-adrenergic ligands, thromboxane, and PKC activator in intact sheep and in isolated vessels [ 231 , 262 , 268 , 269 ]. Therefore, activation of the BK Ca channel could offset vasoconstriction and prevents vasospasm of uterine arteries, which probably contributes to the refractoriness of uterine arteries to vasoconstrictors during normal pregnancy.…”

Section: K Ca Channels and The Uteroplacental Circ...mentioning

confidence: 99%

Ca2+-Activated K+ Channels and the Regulation of the Uteroplacental Circulation

2023

IJMS

Adequate uteroplacental blood supply is essential for the development and growth of the placenta and fetus during pregnancy. Aberrant uteroplacental perfusion is associated with pregnancy complications such as preeclampsia, fetal growth restriction (FGR), and gestational diabetes. The regulation of uteroplacental blood flow is thus vital to the well-being of the mother and fetus. Ca2+-activated K+ (KCa) channels of small, intermediate, and large conductance participate in setting and regulating the resting membrane potential of vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) and play a critical role in controlling vascular tone and blood pressure. KCa channels are important mediators of estrogen/pregnancy-induced adaptive changes in the uteroplacental circulation. Activation of the channels hyperpolarizes uteroplacental VSMCs/ECs, leading to attenuated vascular tone, blunted vasopressor responses, and increased uteroplacental blood flow. However, the regulation of uteroplacental vascular function by KCa channels is compromised in pregnancy complications. This review intends to provide a comprehensive overview of roles of KCa channels in the regulation of the uteroplacental circulation under physiological and pathophysiological conditions.