Hypoxia inhibits vasoconstriction induced by metabotropic Ca2+ channel-induced Ca2+ release in mammalian coronary arteries

We have previously described in rat basilar arterial myocytes that in the absence of extracellular Ca2+ influx, activation of L-type Ca2+ channels stimulates a metabotropic cascade leading to Ca2+ release from the sarcoplasmic reticulum (SR) and contraction [a calcium channel-induced Ca2+ release (CCICR) mechanism]. On the other hand, it is known that hypoxia reduces Ca2+ channel activity in coronary myocytes. In the present study, we have investigated whether CCICR is present in coronary arterial myocytes and whether arterial ring contraction induced by CCICR can be inhibited by hypoxia. Isometric force, arterial diameter, cytosolic [Ca2+] and electrical activity were recorded on mammalian (porcine, rat, and human) coronary artery preparations (dispersed myocytes, arterial rings, and intact arterial segments). In the absence of extracellular Ca2+, Ca2+ channel activation increased cytosolic [Ca2+] in isolated myocytes and contracted arterial rings. This contraction was suppressed by antagonists of L-type Ca2+ channels and by inhibiting Ca2+ release from the SR. Hypoxia induced dilatation of coronary arterial rings pre-contracted by activation of Ca2+ channels in the absence of extracellular Ca2+. This effect was present although K-ATP channels and Rho kinase were blocked by glibenclamide and Y27632, respectively. We show that Ca2+ channel activation can induce metabotropic coronary arterial ring contraction in the absence of extracellular Ca2+ and that this CCICR mechanism is inhibited by hypoxia. Thus, besides reduction of Ca2+ entry through Ca2+ channels, hypoxia seems to induce coronary vasorelaxation by inhibition of metabotropic CCICR.