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 - Edes, Istvan
AU - Bagi, Zsolt
N1 - Funding Information:
This work is supported by grants from the American Heart Association (0735540T) and NIH 43023.
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
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U2 - 10.1093/cvr/cvq088
DO - 10.1093/cvr/cvq088
M3 - Article
C2 - 20299334
AN - SCOPUS:77955887715
SN - 0008-6363
VL - 87
SP - 732
EP - 739
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 4
ER -