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

Abstract

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.

Dietary obesity increases NO and inhibits BKCa-mediated, endothelium-dependent dilation in rat cremaster muscle artery: association with caveolins and caveolae

“…As caveolae are cholesterol-rich, dietary obesity and the accompanying changes in plasma lipid profile could be expected to have an impact on their distribution and function. In coronary arterioles from rats maintained on a high-fat diet (HFD), caveolin-1 expression was decreased and BK Ca -mediated dilation enhanced (20) and similar observations were made in caveolin-1 knockout mice (1,20). It is worth noting these studies measured the expression of caveolin-1 monomer only, rather than the high molecular-weight, oligomerized form of caveolin-1 present in caveolae (35).…”

“…Many of these enzymes and channels are localized within caveolae, as cholesterol-rich invaginations of the plasma membrane (10). Caveolins, the structural proteins of caveolae, have an established role in modulating vascular signaling mechanisms including NO synthase (NOS) and BK Ca activity (1,13,20).Studies on the impact of obesity on endothelium-dependent vasodilation have focused on impaired NO-mediated responses and, in particular, the altered endothelial NOS (eNOS) activity and NO bioavailability associated with inflammatory mediators and oxidative stress (24, 53). Decreased NO-dependent vasodilation, as an apparent consequence of oxidative stress, has been observed in animal models of obesity (16,18,25,26).…”

“…Many of these enzymes and channels are localized within caveolae, as cholesterol-rich invaginations of the plasma membrane (10). Caveolins, the structural proteins of caveolae, have an established role in modulating vascular signaling mechanisms including NO synthase (NOS) and BK Ca activity (1,13,20).…”

Vasorelaxing effects of estetrol in rat arteries

“…Blockade of both K Ca channels results in complete blockade of the EDHF response in rat mesenteric arteries (Crane et al 2003). However, in some arteries, such as skeletal arterioles and coronary arteries, the large-conductance K Ca (BK Ca ) is involved in EDHF-mediated responses (Feher et al 2010). We did not attempt to study the role of the BK Ca channel blocker iberiotoxin in E 4 -and E 2 -mediated relaxing responses in uterine arteries.…”

E-cadherin and caveolin-1 alterations in the heart of rats having undergone chlorpromazine-induced toxicity

“…Excess cav-1 has been reported to play a role in age-dependent hyporesponsiveness to growth factors in vitro (52), and cav-1 interacts with large conductance Ca(2+)-activated potassium channels and likely exerts a negative regulatory effect on the channel activity (53). It has been shown that cav-1 participates in the rapid signaling elicited by the hormone (54).…”