Contractions and relaxations accompanied by endothelial nitric oxide production induced in the porcine coronary artery by Ca2+, Ba2+ and Sr2+.
In order to investigate the effects of Ca2+, Ba2+ and Sr2+ on vascular endothelial nitric oxide (NO) production, contractile and relaxant responses of porcine depolarized coronary arteries to these divalent cations were compared. In the presence of diltiazem, Ba2+ induced NO-dependent relaxation, Sr2+ did slightly and Ca2+ did not; however all three cations increased cGMP levels in endothelium-intact arteries to similar extents. In the absence of diltiazem, these cations evoked contractions: the EC50 of Ca2+ for endothelium-denuded arteries was lower than those of Ba2+ and Sr2+. The IC50 of diltiazem for arteries precontracted with Ca2+ was higher than for arteries precontracted with Ba2+ and Sr2+. These results suggest that Ba2+ and Sr2+, as well as Ca2+, activate coronary arterial NO production, and also that the different responses of coronary arteries to these divalent cations can be explained, in part, by the different sensitivities of the smooth muscle to these cations and by the different potencies of diltiazem to inhibit the contractions the cations induced.
Ohashi
K
K
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Yamazaki
J
J
Nagao
T
T
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000494:pharmacology; D013324:Strontium / Q000494:pharmacology; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology
D002413:Cations, Divalent; D014665:Vasodilator Agents; D001464:Barium; D009569:Nitric Oxide; D004110:Diltiazem; D006152:Cyclic GMP; D002118:Calcium; D013324:Strontium