Hydrogen Sulfide Relaxes Human Uterine Artery by Activating Smooth Muscle BKCa Channels: A Recent Study | Chapter 13 | New Horizons in Medicine and Medical Research Vol. 10

 Background: Vasodilation is mediated by hyperpolarizing smooth muscle (SM) plasma membranes when large conductance calcium-activated and voltage-dependent potassium (BKCa) channels open, which is a critical mechanism for mediating uterine artery (UA) dilatation during pregnancy. Despite the fact that H2S has recently been discovered as a novel UA vasodilator, the mechanisms behind H2S-induced UA dilation remain unexplained.

The goal of this study is to find out how H2S relaxes human UA.

Methods: During a caesarean hysterectomy, pregnant women's main uterine arteries were taken. For electrophysiological experiments, primary smooth muscle cells were extracted and grown. Immunofluorescence microscopy, Western blot, and RT-PCR were used to determine the protein and mRNA expression of BKCa channels. For organ bath experiments, freshly produced uterine artery rings were employed.

Multiple BKCa subunits have been identified in human UA and hUASMC cells in vitro, with high 1and 1proteins localised in SM cells. Iberiotoxin (IBTX) and tetraethylammonium, two BKCa blockers, drastically reduced baseline outward currents. In a dose-dependent manner, H2S enhanced BKCa currents and channel open probability. The Ca2+ blocker nifedipine (5 M) and the chelator ethylene glycol-bis(-aminoethyl ether)-tetraacetic acid (EGTA, 5 mM) had no effect on H2S-potentiated BKCa currents or open probability. NaHS relaxed phenylephrine-pre-constricted newly formed human UA rings in a dose-dependent manner, which was blocked by IBTX.

Conclusions: H2S induces UA relaxation in humans, at least in part, via activating SM BKCa channels that are not reliant on external Ca2+.

Author(S) Details

Yan Li
Department of Obstetrics and Gynecology, University of California, Irvine, CA 92697, USA.

Jin Bai
Department of Obstetrics and Gynecology, University of California, Irvine, CA 92697, USA.

Yi-hua Yang
Department of Obstetrics and Gynecology, University of California, Irvine, CA 92697, USA.

Naoto Hoshi
Department of Pharmacology, University of California, Irvine, CA 92697, USA.

Dong-bao Chen
Department of Obstetrics and Gynecology, University of California, Irvine, CA 92697, USA.

View Book:- https://stm.bookpi.org/NHMMR-V10/article/view/6965

Estrogen Receptors and Estrogen-Induced Uterine Vasodilation in Pregnancy: A Review | Chapter 7 | Current Advances in Chemistry and Biochemistry Vol. 8

 Normal pregnancy is associated with dramatic increases in uterine blood flow to facilitate bidirectional maternal–fetal exchanges of respiratory gases and to provide fetal growth and survival with the sole source of nutrition. The mechanism(s) underlying pregnancy-associated uterine vasodilation are unknown, but it is linked to increased estrogen levels, which stimulate the production of specific estrogen receptor (ER)-dependent vasodilators in the uterine artery (UA). In UA endothelial cells and smooth muscle cells, the classical ERs (ER and ER) and the plasma membrane-bound G protein-coupled ER (GPR30/GPER) are expressed, mediating the estrogenic vasodilatory effects via genomic and/or nongenomic pathways that are likely epigenetically modified The purpose of this chapter is to summarize the literature on UA ERs with a focus on their roles in mediating local UA production of vasodilators by estrogens and pregnancy, as well as to discuss the potential clinical implications of dysregulated ER-mediated estrogen signaling in hypertensive pregnancy complications. The activation of these three ERs by estrogens increases endothelial production of nitric oxide (NO), which has been shown to play a role in uterine contraction. During pregnancy, vasodilation occurs. Local inhibition of NO biosynthesis, on the other hand, only partially attenuates estrogen-induced and pregnancy-associated uterine vasodilation, implying that mechanisms other than NO exist to mediate uterine vasodilation. We review the literature on the role of NO in ER-mediated mechanisms controlling estrogen-induced and pregnancy-associated uterine vasodilation, as well as our recent work on a "new" UA vasodilator, hydrogen sulfide (H2S), which has dramatically altered our understanding of how estrogens regulate uterine vasodilation in pregnancy.

Author(s) Details

Jin Bai
Department of Obstetrics ans Gynecology, University of California, Irvine, CA 92697, USA

Yan Li
Translational Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.

Dr. Ronald R. Magness
Department of Obstetrics and Gynecology, University of South Florida, Tampa, FL 33612, USA.

Dong-bao Chen
Department of Obstetrics ans Gynecology, University of California, Irvine, CA 92697, USA.

View Book :- https://stm.bookpi.org/CACB-V8/article/view/1874