ArticleBritish journal of pharmacology2009
Treatment with the Kv7 potassium channel activator flupirtine is beneficial in two independent mouse models of pulmonary hypertension.
Article in British journal of pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Unleashing the Potential of Nrf2: A Novel Therapeutic Target for Pulmonary Vascular Remodeling.Antioxidants (Basel, Switzerland) · 2023Review
- Mitochondrial Volume Regulation and Swelling Mechanisms in Cardiomyocytes.Antioxidants (Basel, Switzerland) · 2023Review
- Novel Molecular Mechanisms Involved in the Medical Treatment of Pulmonary Arterial Hypertension.International journal of molecular sciences · 2023Review
- Review
- Mechanisms of pulmonary vascular dysfunction in pulmonary hypertension and implications for novel therapies.American journal of physiology. Heart and circulatory physiology · 2022Review
- Role of Ion Channel Remodeling in Endothelial Dysfunction Induced by Pulmonary Arterial Hypertension.Biomolecules · 2022Review
- Kv7 Channels in Cyclic-Nucleotide Dependent Relaxation of Rat Intra-Pulmonary Artery.Biomolecules · 2022Article
- Transcriptomic profile of cationic channels in human pulmonary arterial hypertension.Scientific reports · 2021Article
- Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant Signaling.Antioxidants (Basel, Switzerland) · 2020Review
- Article
- Kv7 Channels in Lung Diseases.Frontiers in physiology · 2020Review
- Activation of KBritish journal of pharmacology · 2019Article
- Ion Channels in Pulmonary Hypertension: A Therapeutic Interest?International journal of molecular sciences · 2018Review
- Zinc pyrithione activates K+ channels and hyperpolarizes the membrane of rat pulmonary artery smooth muscle cells.PloS one · 2018Article
- The Impact of HeterozygousJournal of the American Heart Association · 2017Article
- Kv7 voltage-activated potassium channel inhibitors reduce fluid resuscitation requirements after hemorrhagic shock in rats.Journal of biomedical science · 2017Article
- Update on novel targets and potential treatment avenues in pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- KV7 channels contribute to paracrine, but not metabolic or ischemic, regulation of coronary vascular reactivity in swine.American journal of physiology. Heart and circulatory physiology · 2016Article
- Role of Kv7 channels in responses of the pulmonary circulation to hypoxia.American journal of physiology. Lung cellular and molecular physiology · 2015Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposeVoltage-gated potassium (K(v)) channels contribute to resting membrane potential in pulmonary artery smooth muscle cells and are down regulated in patients with pulmonary arterial hypertension (PAH) and a contribution from K(v)7 channels has been recently proposed. We investigated the effect of the K(v)7 channel activator, flupirtine, on PAH in two independent mouse models: PAH induced by hypoxia and spontaneous PAH in mice over-expressing the 5-HT transporter (SERT(+) mice). EXPERIMENTAL APPROACH: Right ventricular pressure was assessed in vivo in mice chronically treated with flupirtine (30 mg.kg(-1).day(-1)). In separate in vitro experiments, pulmonary arteries from untreated mice were mounted in a wire myograph. Relaxations to acute administration of flupirtine and contractions to K(v) channel blocking drugs, including the K(v)7 channel blocker linopirdine, were measured. KEY
resultsIn wild-type (WT) mice, hypoxia increased right ventricular pressure, pulmonary vascular remodelling and right ventricular hypertrophy. These effects were attenuated by flupirtine, which also attenuated these indices of PAH in SERT(+) mice. In the in vitro experiments, flupirtine induced a potent relaxant response in arteries from untreated WT and SERT(+) mice. The relaxation was fully reversed by linopirdine, which potently contracted mouse pulmonary arteries while other K(v) channel blockers did not. CONCLUSIONS AND IMPLICATIONS: Flupirtine significantly attenuated development of chronic hypoxia-induced PAH in mice and reversed established PAH in SERT(+) mice, apparently via K(v)7 channel activation. These results provide the first direct evidence that drugs activating K(v)7 channels may be of benefit in the treatment of PAH with different aetiologies.
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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.