Role of KCNQ Channels in Skeletal Muscle Arteries and Periadventitial Vascular Dysfunction
Abstract
KCNQ channels have been identified in arterial smooth muscle. However, their role in vasoregulation and chronic vascular diseases remains elusive. We tested the hypothesis that KCNQ channels contribute to periadventitial vasoregulation in peripheral skeletal muscle arteries by perivascular adipose tissue and that they represent novel targets to rescue periadventitial vascular dysfunction. Two models, spontaneously hypertensive rats and New Zealand obese mice, were studied using quantitative polymerase chain reaction, the patch-clamp technique, membrane potential measurements, myography of isolated vessels, and blood pressure telemetry. In rat Gracilis muscle arteries, anticontractile effects of perivascular fat were inhibited by the KCNQ channel blockers XE991 and linopirdine but not by other selective K + channel inhibitors. Accordingly, XE991 and linopirdine blocked noninactivating K + currents in freshly isolated Gracilis artery smooth muscle cells. mRNAs of several KCNQ channel subtypes were detected in those arteries, with KCNQ4 channels being dominant. In spontaneously hypertensive rats, the anticontractile effect of perivascular fat in Gracilis muscle arteries was largely reduced compared with Wistar rats. However, the vasodilator effects of KCNQ channel openers and mRNA expression of KCNQ channels were normal. Furthermore, KCNQ channel openers restored the diminished anticontractile effects of perivascular fat in spontaneously hypertensive rats. Moreover, KCNQ channel openers reduced arterial blood pressure in both models of hypertension independent of ganglionic blockade. Thus, our data suggest that KCNQ channels play a pivotal role in periadventitial vasoregulation of peripheral skeletal muscle arteries, and KCNQ channel opening may be an effective mechanism to improve impaired periadventitial vasoregulation and associated hypertension.
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Targeting these K+ channels is effective in reversing the decline in periadventitial regulation of arterial tone and peripheral resistance in hypertensive rats.
“Moreover, targeting these K+ channels was found effective in reversing the decline in periadventitial regulation of arterial tone and peripheral resistance in hypertensive rats (56).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [56]
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- Authors
- Zavaritskaya, O., Zhuravleva, N., Schleifenbaum, J., Gloe, T., Devermann, L., Kluge, R., Mladenov, M., Frey, M., Gagov, H., Fésüs, G., Gollasch, M., & Schubert, R.
- Affiliations
- Max Delbrück Center (DE)
- From the Centre for Biomedicine and Medical Technology Mannheim, Research Division Cardiovascular Physiology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (O.Z., N.Z., T.G., L.D., M.M., H.G., R.S.); Medical Clinic for Nephrology and Internal Intensive Care, Campus Virchow Klinikum, Experimental and Clinical Research Center and Max-Delbrück Center of Molecular Medicine, Berlin, Germany (N.Z., J.S., G.F., M.G.); Max-Rubner-Laboratory, German Institute of Human Nutrition Potsdam...
- Corresponding author
- Zavaritskaya, Olga
- Zhuravleva, Nadezda
- Gollasch, Maik
- Schubert, Rudolf
- ORCID
- Venue
- Hypertension
- Published
- 2013-01
- Volume
- 61
- Issue
- 1
- Pages
- 151-159
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2160240469
- Cited by
- 70
- References
- 43
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 5 · 2018: 7 · 2017: 10 · 2016: 14 · 2015: 8 · 2014: 9 · 2013: 4
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- OPUS (Augsburg University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- KCNQ channels, KCNQ4, skeletal muscle arteries, perivascular adipose tissue, vascular dysfunction, spontaneously hypertensive rats, obese mice, XE991, linopirdine, smooth muscle cells, vasodilation, blood pressure
- MeSH terms
- Adipose Tissue, Animals, Anthracenes, Arteries, Indoles, Isometric Contraction, Male, Membrane Potentials, Pyridines, Rats, Inbred SHR, Rats, Wistar, Muscle, Skeletal, Potassium Channel Blockers, Mice, Rats, KCNQ Potassium Channels, Arterial Pressure
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