ArticleCirculation research2012
H2O2-induced dilation in human coronary arterioles: role of protein kinase G dimerization and large-conductance Ca2+-activated K+ channel activation.
Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 161 citations in OpenAlex.
- Trial
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- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- The machinery of healthy vasodilatation: an overview.Pflugers Archiv : European journal of physiology · 2025Review
- Overexpression of adipose tissue ERα enhances PVAT anticontractility via NOX4-derived HAmerican journal of physiology. Heart and circulatory physiology · 2025Article
- Sexually dimorphic mechanisms of HJournal of applied physiology (Bethesda, Md. : 1985) · 2025Article
- Renal Medulla in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Redox Regulation of KAntioxidants & redox signaling · 2024Review
- Vasodilator reactive oxygen species ameliorate perturbed myocardial oxygen delivery in exercising swine with multiple comorbidities.Basic research in cardiology · 2024Article
- Study on peripheral antinociception induced by hydrogen peroxide (HNaunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Basal NAD(H) redox state permits hydrogen peroxide-induced mesenteric artery dilatation.The Journal of physiology · 2023Article
- Exercise training rescues impaired HAmerican journal of physiology. Heart and circulatory physiology · 2023Article
- Article
- KCurrent topics in membranes · 2022Review
- Mitochondrial redox regulation and myocardial ischemia-reperfusion injury.American journal of physiology. Cell physiology · 2022Review
- Adenosine and adenosine receptor-mediated action in coronary microcirculation.Basic research in cardiology · 2021Review
- Endothelin-1 potentiates TRPV1-mediated vasoconstriction of human adipose arterioles in a protein kinase C-dependent manner.British journal of pharmacology · 2021Article
- Apelin Does Not Impair Coronary Artery Relaxation Mediated by Nitric Oxide-Induced Activation of BKFrontiers in pharmacology · 2021Article
- Effects of Pharmacological Inhibitors of NADPH Oxidase on Myogenic Contractility and Evoked Vasoactive Responses in Rat Resistance Arteries.Frontiers in physiology · 2021Article
- Importance of cholesterol-rich microdomains in the regulation of Nox isoforms and redox signaling in human vascular smooth muscle cells.Scientific reports · 2020Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
rationaleHydrogen peroxide (H(2)O(2)) serves as a key endothelium-derived hyperpolarizing factor mediating flow-induced dilation in human coronary arterioles (HCAs). The precise mechanisms by which H(2)O(2) elicits smooth muscle hyperpolarization are not well understood. An important mode of action of H(2)O(2) involves the oxidation of cysteine residues in its target proteins, including protein kinase G (PKG)-Iα, thereby modulating their activities.
objectiveHere we hypothesize that H(2)O(2) dilates HCAs through direct oxidation and activation of PKG-Iα leading to the opening of the large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel and subsequent smooth muscle hyperpolarization. METHODS AND
resultsFlow and H(2)O(2) induced pressure gradient/concentration-dependent vasodilation in isolated endothelium-intact and -denuded HCAs, respectively. The dilation was largely abolished by iberiotoxin, a BK(Ca) channel blocker. The PKG inhibitor Rp-8-Br-PET-cGMP also markedly inhibited flow- and H(2)O(2)-induced dilation, whereas the soluble guanylate cyclase inhibitor ODQ had no effect. Treatment of coronary smooth muscle cells (SMCs) with H(2)O(2) elicited dose-dependent, reversible dimerization of PKG-Iα, and induced its translocation to the plasma membrane. Patch-clamp analysis identified a paxilline-sensitive single-channel K(+) current with a unitary conductance of 246-pS in freshly isolated coronary SMCs. Addition of H(2)O(2) into the bath solution significantly increased the probability of BK(Ca) single-channel openings recorded from cell-attached patches, an effect that was blocked by the PKG-Iα inhibitor DT-2. H(2)O(2) exhibited an attenuated stimulatory effect on BK(Ca) channel open probability in inside-out membrane patches.
conclusionsH(2)O(2) dilates HCAs through a novel mechanism involving protein dimerization and activation of PKG-Iα and subsequent opening of smooth muscle BK(Ca) channels.
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