Interspecies Differences and Extracellular Calcium Dependence in the Vasorelaxing Effect of Cromakalim in Isolated Human,Porcine,and Canine Coronary Arteries

Abstract

Coronary arteries isolated from human, porcine, and canine hearts were depolarized with potassium chloride and relaxed by cromakalim (0.0125-10.0 μmol/L) at low (1.5 mmol/L) and high (7.5 mmol/L) extracellular calcium concentration ([Ca²⁺] _o). At low [Ca²⁺]_o, cromakalim (1 μmol/L) relaxed the coronary arteries with the order of porcine > canine > human. Fifty percent effective concentrations of cromakalim revealed the same order: 0.15 μmol/L in porcine, 0.36 μmol/L in canine, and 3.91 μmol/L in human coronary arteries. High [Ca²⁺]_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 [Ca²⁺] _o enhanced the effect of 0.1 μmol/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 [Ca²⁺]_o, with a partly endothelium dependent manner.