Activation of Ca v 1.2 and BK Ca is involved in the downregulation of caffeine-induced contraction in mice mesenteric arteries

Caffeine is a methylxanthine with multiple actions in vascular smooth muscle cells (VSMCs), including the increase in the intracellular Ca ( Ca ) concentration by the activation of ryanodine receptors (RyRs). The present study aimed at investigating the participation of Ca -influx through different...

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Published in:Life sciences (1973) 2019-06, p.116555
Main Authors: Garcia, Daniela C G, Lopes, Miguel J, Mbiakop, Ulrich C, Lemos, Virgínia S, Cortes, Steyner F
Format: Article
Language:English
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Summary:Caffeine is a methylxanthine with multiple actions in vascular smooth muscle cells (VSMCs), including the increase in the intracellular Ca ( Ca ) concentration by the activation of ryanodine receptors (RyRs). The present study aimed at investigating the participation of Ca -influx through different Ca -channels on the transient contraction (TC) induced by caffeine in mice mesenteric arteries. Second-order of mesenteric arteries was isolated from male Swiss mice. Vessels without functional endothelium were stimulated with caffeine (10 mM). The caffeine-induced TC was evaluated after the incubation of artery rings for 30 min with the following drugs: nifedipine (10 μM), a Ca 1.2 blocker; 2-aminoethoxydiphenyl borate (2-APB; 10 μM) and ruthenium red (RuR; 10 μM), transient receptor potential (TRPs) channels blockers; capsazepine (10 μM) and HC067047 (10 μM), TRPV1 and TRPV4 antagonists, respectively; paxilline (1 μM), a selective BK blocker; and SKF-96365 (30 μM), an Orai blocker. Ca -fluorescence measurements were also performed on the investigated arteries. The TC induced by caffeine was partially dependent on Ca -influx. However, the blockage of Ca 1.2 increased the TC while reduced the Ca signal. Similar results were observed after the blockage of TRPs or BK . Therefore, caffeine promoted Ca -influx via TRPs and Ca 1.2, and hyperpolarization through the activation of BK , inducing negative feedback of TC. Our results indicate an alternative mechanism for the control of VSMCs contraction in resistance arteries. The evidence of the negative feedback of contraction via TRP-Ca 1.2-BK provides a new perspective for understanding the mechanism involved in the vascular responses triggered by caffeine.
ISSN:1879-0631