Effects of potassium channel opener aprikalim on the receptor-mediated vasoconstriction in the human internal mammary artery

Background. Arterial grafts for coronary artery bypass grafting such as the internal mammary artery (IMA) may develop spasm perioperatively. The purpo se of this study was to investigate the effects of the potassium channel op ener, aprikalim, on the receptor-mediated vasoconstriction in the human IMA in vitro. Methods. We studied 160 IMA rings taken from coronary artery surgery in org an baths. The interaction between aprikalim and four vasoconstrictors 5-hyd roxytryptamine (5-HT), norepinephrine (NE), endothelin-l (ET-1), and angiot ensin II (AII) was investigated in two ways. Results. Aprikalim relaxed IMA rings precontracted by the vasoconstrictors to 66.40 +/- 5.9% for 5-HT (EC50: -6.78 +/- 0.26 LogM), 57.40 +/- 5.5% for NE (-6.54 +/- 0.39 LogM), 81.00 +/- 6.7% for ET-1 (-6.58 a 0.26 LogM), and 93.90 +/- 2.5% for AII (-7.80 +/- 0.23 LogM). The relaxation in endothelium -denuded rings contracted by AII was similar to that in the endothelium-int act rings. The relaxation was attenuated by glibenclamide (3 muM) in 5-HT o r NE-precontracted IMA. Pretreatment with aprikalim at 1 muM depressed All- induced contraction (33.20 +/- 7.5% versus 59.70 +/- 7.3%, p < 0.01) but on ly shifted the curves rightward for 5-HT or NE (EC50 3.1 or 4.3-folds highe r, p < 0.05), whereas at 30 muM it also significantly depressed the maximal contraction for 5-HT (35.70 +/- 4.9% versus 103.30 +/- 9.8%, p < 0.001) an d NE (90.60 +/- 15.6% versus 125.60 +/- 7.9%,p < 0.05). In contrast, aprika lim did not significantly depress the contraction induced by ET-1 (p > 0.05 ). Conclusions. We conclude that aprikalim has vasorelaxant effects on IMA and the effect is vasoconstrictor-selective and endothelium-independent. Aprik alim may provide clinically useful vasorelaxant effects in coronary bypass surgery. (C) 2001 by The Society of Thoracic Surgeons.