The Effect of Hydroxylamine on K<sub>ATP</sub>Channels in Vascular Smooth Muscle and Underlying Mechanisms

Tang, Guanghua; Wu, Lin‐Sheng; Wang, Rui

doi:10.1124/mol.104.008953

Cited by 17 publications

(8 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hcy at a concentration range of 1, 100, and 300 lM did not alter the amplitude of outward K + currents (n = 5-8 for each concentration, Fig. Another way to increase the concentration of superoxide radicals is to add a free radical generation system-a mixture of hypoxanthine (HX, 100 lM) and xanthine oxidase (XO, 0.01 UÁmL À1 ) [24]. In porcine coronary artery smooth muscle cells it was reported that Hcy was effective only in the presence of NADH in the pipette a substrate of NADH-oxidases, generating superoxide anions [11].…”

Section: Resultsmentioning

confidence: 99%

Homocysteine augments BK channel activity and decreases exocytosis of secretory granules in rat GH3 cells

et al. 2016

View full text Add to dashboard Cite

In this study, we investigated the effects of L-homocysteine (Hcy) on maxi calcium-activated potassium (BK) channels and on exocytosis of secretory granules in GH3 rat pituitary-derived cells. A major finding of our study indicates that short-term application of Hcy increased the open probability of oxidized BK channels in inside-out recordings. Whole-cell recordings show that extracellular Hcy also augmented BK currents during long-term application. Furthermore, Hcy decreased the exocytosis of secretory granules. This decrease was partially prevented by the BK channel inhibitor paxilline and fully prevented by N-acetylcysteine, a reactive oxygen species scavenger. Taken together, our data show that elevation of cellular Hcy level induces oxidative stress, increases BK channel activity, and decreases exocytosis of secretory granules. These findings may provide insight into some of the developmental impairments and neurotoxicity associated with Hyperhomocysteinemia (HHcy), a disease arising due to abnormally elevated levels of Hcy in the plasma.

show abstract

Section: Resultsmentioning

confidence: 99%

Homocysteine augments BK channel activity and decreases exocytosis of secretory granules in rat GH3 cells

et al. 2016

View full text Add to dashboard Cite

show abstract

“…H 2 S is a vasorelaxant factor that acts through K ATP channels causing smooth muscle relaxation 1,41 and playing a role in uterine contractility. 27 Recent placental studies provided contradictory findings probably because of the small sample size of these studies.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of Hydrogen Sulfide Producing Enzyme Cystathionine γ-lyase Contributes to Maternal Hypertension and Placental Abnormalities in Preeclampsia

et al. 2013

Self Cite

View full text Add to dashboard Cite

H ydrogen sulfide (H 2 S), a gaseous signaling molecule, promotes vasodilatation 1 and stimulates angiogenesis in the vasculature.2 H 2 S has anti-inflammatory properties 3 and is also cytoprotective against cellular damage induced by lethal hypoxia or reperfusion injury. 4,5 Cystathionine γ-lyase (CSE) is the principal enzyme responsible for the endogenous production of H 2 S.6 Chronic administration of the CSE inhibitor DL-propargylglycine (PAG) leads to elevated blood pressure and vascular remodeling in the rat, 7 and both CSE and H 2 S levels are reduced in pulmonary hypertensive rats. 8Mice genetically deficient in CSE develop age-dependent hypertension, severe hyperhomocysteinemia, and endothelial dysfunction. 9 Clearly, H 2 S has multiple roles in health and disease, 10,11 but its role in pregnancy-induced hypertension is unknown. Editorial see p 2472 Clinical Perspective on p 2522Preeclampsia is a hypertensive syndrome that affects 4% to 7% of all pregnancies and is a major contributor to maternal and fetal morbidity and mortality worldwide. 12 The exact etiology of preeclampsia is unknown; abnormal placentation 13,14 and imbalance in angiogenic factors 15,16 have been implicated in preeclampsia pathogenesis. Importantly, circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1), the endogenous inhibitor of vascular endothelial growth factor and placental Background-The exact etiology of preeclampsia is unknown, but there is growing evidence of an imbalance in angiogenic growth factors and abnormal placentation. Hydrogen sulfide (H 2 S), a gaseous messenger produced mainly by cystathionine γ-lyase (CSE), is a proangiogenic vasodilator. We hypothesized that a reduction in CSE activity may alter the angiogenic balance in pregnancy and induce abnormal placentation and maternal hypertension. Methods and Results-Plasma levels of H 2 S were significantly decreased in women with preeclampsia (P<0.01), which was associated with reduced placental CSE expression as determined by real-time polymerase chain reaction and immunohistochemistry. Inhibition of CSE activity by DL-propargylglycine reduced placental growth factorproduction from first-trimester (8-12 weeks gestation) human placental explants and inhibited trophoblast invasion in vitro. Knockdown of CSE in human umbilical vein endothelial cells by small-interfering RNA increased the release of soluble fms-like tyrosine kinase-1 and soluble endoglin, as assessed by enzyme-linked immunosorbent assay, whereas adenoviral-mediated CSE overexpression in human umbilical vein endothelial cells inhibited their release. Administration of DL-propargylglycine to pregnant mice induced hypertension and liver damage, promoted abnormal labyrinth vascularization in the placenta, and decreased fetal growth. Finally, a slow-releasing H 2 S-generating compound, GYY4137, inhibited circulating soluble fms-like tyrosine kinase-1 and soluble endoglin levels and restored fetal growth in mice that was compromised by DL-propargylglycine treatment, demonstrating that the effect ...

show abstract

“…In some animals, such as the mouse, K ATP channels are not involved at all in the response. H 2 S may also signal via other pathways, such as activation of adenylate cyclase, which, in turn, inhibits superoxide formation, NADPH oxidase, and Rac 1 activity (112); it may produce intracellular acidosis and alter intracellular redox status, stimulate an anion exchanger (97), or operate through Ca 2ϩ -dependent K ϩ (K Ca ) channels (77,161,206). Relaxation of rat aorta by exogenous H 2 S does not depend on vascular prostaglandin synthesis, PKC, or cAMP, nor does it involve superoxide or H 2 O 2 production (77,78,204).…”

Section: H 2 S Biologymentioning

confidence: 99%

The therapeutic potential of hydrogen sulfide: separating hype from hope

Olson

2011

American Journal of Physiology-Regulatory, Integrative and Comp

162

154

View full text Add to dashboard Cite

Hydrogen sulfide (H2S) has become the hot new signaling molecule that seemingly affects all organ systems and biological processes in which it has been investigated. It has also been shown to have both proinflammatory and anti-inflammatory actions and proapoptotic and anti-apoptotic effects and has even been reported to induce a hypometabolic state (suspended animation) in a few vertebrates. The exuberance over potential clinical applications of natural and synthetic H2S-“donating” compounds is understandable and a number of these function-targeted drugs have been developed and show clinical promise. However, the concentration of H2S in tissues and blood, as well as the intrinsic factors that affect these levels, has not been resolved, and it is imperative to address these points to distinguish between the physiological, pharmacological, and toxicological effects of this molecule. This review will provide an overview of H2S metabolism, a summary of many of its reported “physiological” actions, and it will discuss the recent development of a number of H2S-donating drugs that show clinical potential. It will also examine some of the misconceptions of H2S chemistry that have appeared in the literature and attempt to realign the definition of “physiological” H2S concentrations upon which much of this exuberance has been established.

show abstract

The Effect of Hydroxylamine on K_ATPChannels in Vascular Smooth Muscle and Underlying Mechanisms

Cited by 17 publications

References 37 publications

Homocysteine augments BK channel activity and decreases exocytosis of secretory granules in rat GH3 cells

Homocysteine augments BK channel activity and decreases exocytosis of secretory granules in rat GH3 cells

Dysregulation of Hydrogen Sulfide Producing Enzyme Cystathionine γ-lyase Contributes to Maternal Hypertension and Placental Abnormalities in Preeclampsia

The therapeutic potential of hydrogen sulfide: separating hype from hope

Contact Info

Product

Resources

About

The Effect of Hydroxylamine on KATPChannels in Vascular Smooth Muscle and Underlying Mechanisms

Cited by 17 publications

References 37 publications

Homocysteine augments BK channel activity and decreases exocytosis of secretory granules in rat GH3 cells

Homocysteine augments BK channel activity and decreases exocytosis of secretory granules in rat GH3 cells

Dysregulation of Hydrogen Sulfide Producing Enzyme Cystathionine γ-lyase Contributes to Maternal Hypertension and Placental Abnormalities in Preeclampsia

The therapeutic potential of hydrogen sulfide: separating hype from hope

Contact Info

Product

Resources

About

The Effect of Hydroxylamine on K_ATPChannels in Vascular Smooth Muscle and Underlying Mechanisms