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001-es BibID:BIBFORM018438
Első szerző:Fehér Attila (orvos)
Cím:Caveolin-1 limits the contribution of BK(Ca) channel to EDHF-mediated arteriolar dilation: implications in diet-induced obesity / Feher, A., Rutkai, I., Beleznai, T., Ungvari, Z., Csiszar, A., Edes, I., Bagi, Z.
Dátum:2010
ISSN:0008-6363
Megjegyzések: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 (approximately 100 microm) 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-beta-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.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Coronary
Microcirculation
EDHF
MaxiK channel
Caveolae
Megjelenés:Cardiovascular Research. - 87 : 4 (2010), p. 732-739. -
További szerzők:Rutkai Ibolya (1985-) (molekuláris biológus) Beleznai Tímea (1981-) (orvos) Ungvári Zoltán Csiszár Anna Édes István (1952-) (kardiológus) Bagi Zsolt (1974-) (orvos)
Pályázati támogatás:0735540T
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