Role of store-operated Ca²⁺ entry in adenosine-induced vasodilatation of rat small mesenteric artery

Abstract

Store-operated Ca(2+) entry (SOCE) has recently been proposed to contribute to Ca(2+) influx in vascular smooth muscle cells (VSMCs). Adenosine is known for its protective role against hypoxia and ischemia by increasing nutrient and oxygen supply through vasodilation. This study was designed to examine the hypothesis that SOCE have a functional role in adenosine-induced vasodilation. Small mesenteric resistance arteries and mesenteric VSMCs were obtained from rats. Isometric tensions of isolated artery rings were measured by a sensitive myograph system. Laser-scanning confocal microscopy was used to determine the intracellular Ca(2+) concentration of fluo 3-loaded VSMCs. Adenosine (0.1-100 microM) relaxed artery rings that were precontracted by phenylephrine in a concentration-dependent manner. In cultured mesenteric VSMCs, passive store depletion by thapsigargin and active store depletion by phenylephrine both induced Ca(2+) influx due to SOCE. Adenosine inhibited SOCE-mediated increases in cytosolic Ca(2+) levels evoked by the emptying of the stores. In isolated artery rings, adenosine inhibited SOCE-induced contractions due to store depletion. A(2A) receptor antagonism with SCH-58261 and adenylate cyclase inhibition with SQ-22536 largely attenuated adenosine responses. The cAMP analog 8-bromo-cAMP mimicked the effects of adenosine on SOCE. Our results indicate a novel mechanism of vasodilatation by adenosine that involves regulation of SOCE through the cAMP signaling pathway due to activation of adenosine A(2A) receptors.

Purinergic Signaling and Blood Vessels in Health and Disease

“…In contrast, studies carried out in rat small mesenteric arteries showed that smooth muscle relaxation by adenosine may involve A 2A receptors that inhibit store-operated Ca 2+ entry-mediated increases in cytosolic Ca 2+ levels enhanced by the emptying of the stores (Wang et al, 2009c). A 2B receptors are the prominent P1 receptor subtype in mouse mesenteric arterial smooth muscle, whereas A 1 receptors play a modulatory role (Teng et al, 2013).…”

Exercise improves the dilatation function of mesenteric arteries in postmyocardial infarction rats via a PI3K/Akt/eNOS pathway-mediated mechanism

“…Removal of the endothelium was confirmed by a lack of relaxation response to 1 M ACh. Isometric tension was measured as previously described (45). Briefly, arterial rings (internal diameter ϳ150 m) were mounted in a Multi Myograph System (Danish Myo Technology A/S, Aarhus, Denmark), and changes in isometric tension were continually recorded.…”

Mechanisms involved in the adenosine-induced vasorelaxation to the pig prostatic small arteries

“…Thus, adenosine A 2A receptors have been described in coronary vessels from rat mesenteric arteries [30], while adenosine A 2B receptors mediate vasorelaxation of human coronary arteries [31]. It has recently been suggested that there is a compensatory upregulation of the adenosine A 2B receptor in an adenosine A 2A receptor knock-out mouse model [32].…”