ArticleBritish journal of pharmacology2003
Selective blockade of endothelial Ca2+-activated small- and intermediate-conductance K+-channels suppresses EDHF-mediated vasodilation.
Article in British journal of pharmacology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 171 citations in OpenAlex.
- Pravastatin Corrects Endothelial Dysfunction in Ex Vivo Uterine Radial Arteries in Preeclampsia.Acta physiologica (Oxford, England) · 2026Trial
- Bilobalide increases SKBMC complementary medicine and therapies · 2026Article
- Editorial: Integrative endothelial signaling mechanisms in resistance arteries.Frontiers in physiology · 2026Article
- The exocyst complex is required for the trafficking and delivery of KCa3.1 to the basolateral membrane of polarized epithelia.American journal of physiology. Cell physiology · 2023Article
- CaInternational journal of molecular sciences · 2023Review
- Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function.International journal of molecular sciences · 2022Review
- Role of Ion Channel Remodeling in Endothelial Dysfunction Induced by Pulmonary Arterial Hypertension.Biomolecules · 2022Review
- Effect of the KCa3.1 blocker, senicapoc, on cerebral edema and cardiovascular function after cardiac arrest - A randomized experimental rat study.Resuscitation plus · 2021Article
- Calcium-Dependent Ion Channels and the Regulation of Arteriolar Myogenic Tone.Frontiers in physiology · 2021Review
- Novel Pannexin-1-Coupled Signaling Cascade Involved in the Control of Endothelial Cell Function and NO-Dependent Relaxation.Oxidative medicine and cellular longevity · 2021Article
- Polarized Proteins in Endothelium and Their Contribution to Function.Journal of vascular research · 2021Review
- Contribution of the Potassium Channels KCells · 2020Article
- Calcium signals that determine vascular resistance.Wiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- CGRP signalling inhibits NO production through pannexin-1 channel activation in endothelial cells.Scientific reports · 2019Article
- Extracellular l-arginine Enhances Relaxations Induced by Opening of Calcium-Activated SKCa Channels in Porcine Retinal Arteriole.International journal of molecular sciences · 2019Article
- The potential role of testosterone in hypertension and target organ damage in hypertensive postmenopausal women.Clinical interventions in aging · 2019Article
- Connexins and Pannexins in Vascular Function and Disease.International journal of molecular sciences · 2018Review
- Overview of the Microenvironment of Vasculature in Vascular Tone Regulation.International journal of molecular sciences · 2018Review
- Article
- Role of the endothelial caveolae microdomain in shear stress-mediated coronary vasorelaxation.The Journal of biological chemistry · 2017Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. Activation of Ca(2+)-activated K(+)-channels (K(Ca)) has been suggested to play a key role in endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilation. However, due to the low selectivity of commonly used K(Ca)-channel blockers it is still elusive which endothelial K(Ca)-subtypes mediate hyperpolarization and thus initiate EDHF-mediated vasodilation. 2. Using the non-cytochrome P450 blocking clotrimazole-derivatives, 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) and 2-(2-chlorophenyl)-2,2-diphenylacetonitrile (TRAM-39) as highly selective IK1-inhibitors, we investigated the role of the intermediate-conductance K(Ca) (rIK1) in endothelial hyperpolarization and EDHF-mediated vasodilation. 3. Expression and function of rIK1 and small-conductance K(Ca) (rSK3) were demonstrated in situ in single endothelial cells of rat carotid arteries (CA). rIK1-currents were blocked by TRAM-34 or TRAM-39, while rSK3 was blocked by apamin. In current-clamp experiments, endothelial hyperpolarization in response to acetylcholine was abolished by the combination of apamin and TRAM-34. 4. In phenylephrine-preconstricted CA, acetylcholine-induced NO and prostacyclin-independent vasodilation was almost completely blocked by ChTX, CLT, TRAM-34, or TRAM-39 in combination with the SK3-blocker apamin. Apamin, TRAM-34, and CLT alone or sulphaphenzole, a blocker of the cytochrome P450 isoform 2C9, were ineffective in blocking the EDHF-response. 5. In experiments without blocking NO and prostacyclin synthesis, the combined blockade of SK3 and IK1 reduced endothelium-dependent vasodilation. 6. In conclusion, the use of selective IK1-inhibitors together with the SK3-blocker apamin revealed that activation of both K(Ca), rIK1 and rSK3 is crucial in mediating endothelial hyperpolarization and generation of the EDHF-signal while the cytochrome P450 pathway seems to play a minor or no role in rat CA.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.