Caveolar disruption with methyl-β-cyclodextrin causes endothelium-dependent contractions in Wistar rat carotid arteries
2022
Albrakati, Ashraf
Caveolae are organizing centers for cellular signal transduction in endothelial cells (ED) and smooth muscle cells (SMCs) in the blood vessels. Myography was used to investigate the effects of a caveolar disruption using methyl-β-cyclodextrin (MBCD) on maxi-K channels in rat carotid arteries. Incubation of carotid segments with MBCD augmented contractions in response to BaK (chemical channel agonist) but not those induced by depolarizing high potassium physiological saline (KPSS). In contrast, incubation with cholesterol-saturated MBCD (Ch-MBCD) abolished the effects of MBCD. Mechanical removal of endothelial cells by MBCD triggered a small contraction in response to BaK. Incubation with nitroarginine methyl ester (L-NAME) inhibited nitric oxide (NO) release, causing increased contractions in response to BaK, and this effect was reversed by pretreatment with MBCD. These results suggest that MBCD inhibits endothelial NO release. Contrastingly, inhibition of maxi-K channels with iberiotoxin enhanced contractions in response to BaK. Likewise, L-NAME decreased the contractile effect of iberiotoxin, as in the ED-denuded arteries. Transmission electron microscopy (TEM) showed the presence and absence of caveolae in intact blood vessels before and after MBCD treatment, respectively, whereas histology confirmed ED removal after the treatment. Caveolar disruption using MBCD impairs ED-dependent relaxation by inhibiting the release of NO from the ED and altered the contractility of SMCs independent of the ED due to reduced contribution of maxi-K channels to the SMC membrane potential, causing depolarization and increasing carotid artery contraction. These findings might help to understand the physiological role of the maxi-K channels in rat carotid arteries.
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