Hypoxia inhibits vasoconstriction induced by metabotropic Ca2+ channel-induced Ca2+ release in mammalian coronary arteries.
OBJECTIVE
We have previously described in rat basilar arterial myocytes that in the absence of extracellular Ca(2+) influx, activation of L-type Ca(2+) channels stimulates a metabotropic cascade leading to Ca(2+) release from the sarcoplasmic reticulum (SR) and contraction [a calcium channel-induced Ca(2+) release (CCICR) mechanism]. On the other hand, it is known that hypoxia reduces Ca(2+) 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.


RESULTS
Isometric force, arterial diameter, cytosolic [Ca(2+)] 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 Ca(2+), Ca(2+) channel activation increased cytosolic [Ca(2+)] in isolated myocytes and contracted arterial rings. This contraction was suppressed by antagonists of L-type Ca(2+) channels and by inhibiting Ca(2+) release from the SR. Hypoxia induced dilatation of coronary arterial rings pre-contracted by activation of Ca(2+) channels in the absence of extracellular Ca(2+). This effect was present although K(ATP) channels and Rho kinase were blocked by glibenclamide and Y27632, respectively.


CONCLUSIONS
We show that Ca(2+) channel activation can induce metabotropic coronary arterial ring contraction in the absence of extracellular Ca(2+) and that this CCICR mechanism is inhibited by hypoxia. Thus, besides reduction of Ca(2+) entry through Ca(2+) channels, hypoxia seems to induce coronary vasorelaxation by inhibition of metabotropic CCICR.
Calderón-Sánchez
Eva
E
Instituto de Biomedicina de Sevilla , Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Avenida Manuel Siurot s/n, Seville E-41013, Spain.
Fernández-Tenorio
Miguel
M
Ordóñez
Antonio
A
López-Barneo
José
J
Ureña
Juan
J
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D015687:Cell Hypoxia; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D054086:KATP Channels; D026902:Potassium Channel Blockers; D047428:Protein Kinase Inhibitors; D054460:rho-Associated Kinases; D011188:Potassium