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, I. Édes, Zsolt Bagi

Research output: Article

31 Citations (Scopus)

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
Pages (from-to)732-739
Number of pages8
JournalCardiovascular Research
Volume87
Issue number4
DOIs
Publication statusPublished - szept. 1 2010

Fingerprint

Large-Conductance Calcium-Activated Potassium Channels
Caveolin 1
Endothelium
Dilatation
Obesity
Diet
Acetylcholine
Arterioles
Knockout Mice
Caveolae
Potassium Channels
Cyclodextrins
High Fat Diet
Vasodilation
Theoretical Models
Western Blotting
Immunohistochemistry
iberiotoxin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Caveolin-1 limits the contribution of BK(Ca) channel to EDHF-mediated arteriolar dilation : Implications in diet-induced obesity. / Feher, Attila; Rutkai, Ibolya; Beleznai, Timea; Ungvari, Zoltan; Csiszar, Anna; Édes, I.; Bagi, Zsolt.

In: Cardiovascular Research, Vol. 87, No. 4, 01.09.2010, p. 732-739.

Research output: Article

Feher, Attila ; Rutkai, Ibolya ; Beleznai, Timea ; Ungvari, Zoltan ; Csiszar, Anna ; Édes, I. ; Bagi, Zsolt. / Caveolin-1 limits the contribution of BK(Ca) channel to EDHF-mediated arteriolar dilation : Implications in diet-induced obesity. In: Cardiovascular Research. 2010 ; Vol. 87, No. 4. pp. 732-739.
@article{7a39b4d93b50402f86f778d5f0a6c1ab,
title = "Caveolin-1 limits the contribution of BK(Ca) channel to EDHF-mediated arteriolar dilation: Implications in diet-induced obesity",
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.",
keywords = "Caveolae, Coronary, EDHF, MaxiK channel, Microcirculation",
author = "Attila Feher and Ibolya Rutkai and Timea Beleznai and Zoltan Ungvari and Anna Csiszar and I. {\'E}des and Zsolt Bagi",
year = "2010",
month = "9",
day = "1",
doi = "10.1093/cvr/cvq088",
language = "English",
volume = "87",
pages = "732--739",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Caveolin-1 limits the contribution of BK(Ca) channel to EDHF-mediated arteriolar dilation

T2 - Implications in diet-induced obesity

AU - Feher, Attila

AU - Rutkai, Ibolya

AU - Beleznai, Timea

AU - Ungvari, Zoltan

AU - Csiszar, Anna

AU - Édes, I.

AU - Bagi, Zsolt

PY - 2010/9/1

Y1 - 2010/9/1

N2 - 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.

AB - 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.

KW - Caveolae

KW - Coronary

KW - EDHF

KW - MaxiK channel

KW - Microcirculation

UR - http://www.scopus.com/inward/record.url?scp=77955887715&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955887715&partnerID=8YFLogxK

U2 - 10.1093/cvr/cvq088

DO - 10.1093/cvr/cvq088

M3 - Article

C2 - 20299334

AN - SCOPUS:77955887715

VL - 87

SP - 732

EP - 739

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 4

ER -