Caveolin-1 limits the contribution of BK(Ca) channel to EDHF-mediated arteriolar dilation: Implications in diet-induced obesity

Attila Feher, Ibolya Rutkai, Timea Beleznai, Zoltan Ungvari, Anna Csiszar, Istvan Edes, Zsolt Bagi

32 Scopus citations

Abstract

Aims Caveolin-1 (Cav-1) interacts with large conductance Ca 2+-activated potassium channels (BKCa) and likely exerts a negative regulatory effect on the channel activity. We investigated the role of Cav-1 in modulating BK(Ca) channel-mediated, endothelium-derived hyperpolarizing factor (EDHF)-dependent arteriolar dilation in normal condition and in an experimental model of obesity. Methods and results In isolated, pressurized (80 mmHg) gracilis muscle arterioles (∼100 m) of Cav-1 knockout mice, acetylcholine (ACh)-induced, EDHF-mediated dilations were enhanced and were significantly reduced by the BK(Ca) channel inhibitor, iberiotoxin (IBTX), whereas IBTX had no effect on EDHF-mediated dilations in the wild-type mice. Dilations to the selective BK(Ca) channel opener, NS-1619 were augmented in the Cav-1 knockout mice. In high-fat diet-treated, obese rats ACh-induced coronary arteriolar dilations were preserved, whereas IBTX-sensitive, ACh-induced and also NS-1619-evoked vasodilations were augmented when compared with lean animals. In coronary arterioles of obese rats a reduced protein expression of Cav-1 was detected by western immunoblotting and immunohistochemistry. Moreover, in coronary arterioles of lean rats, disruption of caveolae with methyl-cyclodextrin augmented IBTX-sensitive, ACh-induced, and also NS-1619-evoked dilations. Conclusion Thus, under normal conditions, Cav-1 limits the contribution of the BK(Ca) channel to EDHF-mediated arteriolar dilation. In obesity, a reduced expression of Cav-1 leads to greater contribution of the BK(Ca) channel to EDHF-mediated response, which seems essential for maintained coronary dilation.

Original languageEnglish (US)
Pages (from-to)732-739
Number of pages8
JournalCardiovascular Research
Volume87
Issue number4
DOIs
Publication statusPublished - Sep 1 2010
Externally publishedYes

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