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Ann Thorac Surg 2001;71:636-641
© 2001 The Society of Thoracic Surgeons

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Original article: cardiovascular

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

^a Cardiovascular Research, Starr Academic Center for Cardiac Surgery, Providence Heart Institute, St. Vincent Hospital, Portland, Oregon, USA
^b Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China

Accepted for publication June 3, 2000.

Address reprint requests to Prof. He, Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Block B, 5A, Prince of Wales Hospital, Shatin, N.T., Hong Kong SAR, China
e-mail: gwhe{at}cuhk.edu.hk

Background. Arterial grafts for coronary artery bypass grafting such as the internal mammary artery (IMA) may develop spasm perioperatively. The purpose of this study was to investigate the effects of the potassium channel opener, aprikalim, on the receptor-mediated vasoconstriction in the human IMA in vitro.

Methods. We studied 160 IMA rings taken from coronary artery surgery in organ baths. The interaction between aprikalim and four vasoconstrictors 5-hydroxytryptamine (5-HT), norepinephrine (NE), endothelin-1 (ET-1), and angiotensin 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 ± 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-intact rings. The relaxation was attenuated by glibenclamide (3 µM) in 5-HT or NE-precontracted IMA. Pretreatment with aprikalim at 1 µM depressed AII-induced contraction (33.20 ± 7.5% versus 59.70 ± 7.3%, p < 0.01) but only shifted the curves rightward for 5-HT or NE (EC₅₀ 3.1 or 4.3-folds higher, p < 0.05), whereas at 30 µM it also significantly depressed the maximal contraction for 5-HT (35.70 ± 4.9% versus 103.30 ± 9.8%, p < 0.001) and NE (90.60 ± 15.6% versus 125.60 ± 7.9%, p < 0.05). In contrast, aprikalim 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. Aprikalim may provide clinically useful vasorelaxant effects in coronary bypass surgery.

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