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Role of KCNQ channels in skeletal muscle arteries and periadventitial vascular dysfunction

Item Type:Article
Title:Role of KCNQ channels in skeletal muscle arteries and periadventitial vascular dysfunction
Creators Name:Zavaritskaya, O. and Zhuravleva, N. and Schleifenbaum, J. and Gloe, T. and Devermann, L. and Kluge, R. and Mladenov, M. and Frey, M. and Gagov, H. and Fesues, G. and Gollasch, M. and Schubert, R.
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.
Keywords:Adipocyte-Derived Relaxing Factor, Obesity Hypertension, Vascular Dysfunction, KCNQ Channels, Animals, Rats
Publisher:American Heart Association
Page Range:151-159
Date:January 2013
Official Publication:https://doi.org/10.1161/HYPERTENSIONAHA.112.197566
PubMed:View item in PubMed

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