Interspecies differences and extracellular calcium dependence in the vasorelaxing effect of cromakalim in isolated human, porcine, and canine coronary arteries.
Coronary arteries isolated from human, porcine, and canine hearts were depolarized with potassium chloride and relaxed by cromakalim (0.0125-10.0 micromol/L) at low (1.5 mmol/L) and high (7.5 mmol/L) extracellular calcium concentration ([Ca(2+)]( o)). At low [Ca(2+)](o), cromakalim (1 micromol/L) relaxed the coronary arteries with the order of porcine > canine > human. Fifty percent effective concentrations of cromakalim revealed the same order: 0.15 micromol/L in porcine, 0.36 micromol/L in canine, and 3.91 micromol/L in human coronary arteries. High [Ca(2+)](o) significantly enhanced the relaxing effect and decreased the potency of cromakalim in porcine and human but not in canine coronary arteries. In human coronary arteries, precontracted with the prostaglandin analogue (U46619), high [Ca(2+)]( o) enhanced the effect of 0.1 micromol/L cromakalim more efficiently in the presence than in the absence of endothelium. It appears that the coronary dilating effect of cromakalim largely depends on the species and is modulated by [Ca(2+)](o,) with a partly endothelium dependent manner.
Pataricza
János
J
Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical Centre, University of Szeged, Szeged, Hungary. Pataricza@phcol.szote.u-szeged.hu
Krassói
Irén
I
Ambrus
Nora
N
Bitay
Miklós
M
Varró
András
A
Papp
Julius Gyula
JG
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D019806:Cromakalim / Q000494:pharmacology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D013045:Species Specificity; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019806:Cromakalim; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002118:Calcium