ArticlePloS one2014
Upregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Obesity-Associated Adiposomes Promote Vascular Smooth Muscle Cell Hypercontractility.Comprehensive Physiology · 2025Article
- Ginsenoside Re increases human coronary artery endothelial SKJournal of ginseng research · 2025Article
- NONO2P, a nitric oxide donor, induces relaxation in coronary artery, negative inotropism and hypotensive effect in rats.Biochemical pharmacology · 2025Article
- LDL-c/HDL-c Ratio and NADPH-Oxidase-2-Derived Oxidative Stress as Main Determinants of Microvascular Endothelial Function in Morbidly Obese Subjects.Antioxidants (Basel, Switzerland) · 2024Article
- Impact of aging on vascular ion channels: perspectives and knowledge gaps across major organ systems.American journal of physiology. Heart and circulatory physiology · 2023Review
- Molecular mechanisms of endothelial dysfunction in coronary microcirculation dysfunction.Journal of thrombosis and thrombolysis · 2023Review
- Upregulation of Orai Channels Contributes to Aging-Related Vascular Alterations in Rat Coronary Arteries.International journal of molecular sciences · 2023Article
- The Long-Term Effects of Prenatal Hypoxia on Coronary Artery Function of the Male and Female Offspring.Biomedicines · 2022Article
- A comparative pharmacogenomic analysis of three classic TCM prescriptions for coronary heart disease based on molecular network modeling.Acta pharmacologica Sinica · 2020Article
- Plasma protein(s)-based conceptual diagnostic tool for assessing high-altitude acclimation in humans.Functional & integrative genomics · 2020Article
- Experimental animal models of coronary microvascular dysfunction.Cardiovascular research · 2020Review
- Type 2 Diabetes Alters Intracellular CaInternational journal of molecular sciences · 2019Article
- Endothelium-Dependent Hyperpolarization (EDH) in Diabetes: Mechanistic Insights and Therapeutic Implications.International journal of molecular sciences · 2019Review
- Functional Interaction among KInternational journal of molecular sciences · 2019Review
- Pharmacologic targeting of endothelial CaChannels (Austin, Tex.) · 2018Review
- Impact of Aging on Calcium Signaling and Membrane Potential in Endothelium of Resistance Arteries: A Role for Mitochondria.The journals of gerontology. Series A, Biological sciences and medical sciences · 2017Article
- Calcium and electrical signaling in arterial endothelial tubes: New insights into cellular physiology and cardiovascular function.Microcirculation (New York, N.Y. : 1994) · 2017Review
- Augmented oxidative stress and preserved vasoconstriction induced by hydrogen peroxide in coronary arteries in obesity: role of COX-2.British journal of pharmacology · 2016Article
- KCa 3.1 upregulation preserves endothelium-dependent vasorelaxation during aging and oxidative stress.Aging cell · 2016Article
- Vascular Reactivity Profile of Novel KCa 3.1-Selective Positive-Gating Modulators in the Coronary Vascular Bed.Basic & clinical pharmacology & toxicology · 2016Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsEndothelial small- and intermediate-conductance KCa channels, SK3 and IK1, are key mediators in the endothelium-derived hyperpolarization and relaxation of vascular smooth muscle and also in the modulation of endothelial Ca2+ signaling and nitric oxide (NO) release. Obesity is associated with endothelial dysfunction and impaired relaxation, although how obesity influences endothelial SK3/IK1 function is unclear. Therefore we assessed whether the role of these channels in the coronary circulation is altered in obese animals. METHODS AND
resultsIn coronary arteries mounted in microvascular myographs, selective blockade of SK3/IK1 channels unmasked an increased contribution of these channels to the ACh- and to the exogenous NO- induced relaxations in arteries of Obese Zucker Rats (OZR) compared to Lean Zucker Rats (LZR). Relaxant responses induced by the SK3/IK1 channel activator NS309 were enhanced in OZR and NO- endothelium-dependent in LZR, whereas an additional endothelium-independent relaxant component was found in OZR. Fura2-AM fluorescence revealed a larger ACh-induced intracellular Ca2+ mobilization in the endothelium of coronary arteries from OZR, which was inhibited by blockade of SK3/IK1 channels in both LZR and OZR. Western blot analysis showed an increased expression of SK3/IK1 channels in coronary arteries of OZR and immunohistochemistry suggested that it takes place predominantly in the endothelial layer.
conclusionsObesity may induce activation of adaptive vascular mechanisms to preserve the dilator function in coronary arteries. Increased function and expression of SK3/IK1 channels by influencing endothelial Ca2+ dynamics might contribute to the unaltered endothelium-dependent coronary relaxation in the early stages of obesity.
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