INTERACTION BETWEEN ENDOTHELIN AND VASODILATORS IN THE HUMAN INTERNAL MAMMARY ARTERY

1 The internal mammary artery (IMA) is the primary choice as an arterial graft for coronary artery bypass surgery. Endothelin (ET) has been recently measured with an increased release after cardiopulmonary bypass for coronary artery bypass grafting. Threshold concentrations of ET-1 have been found to amplify specifically contractions induced by noradrenaline and serotonin. This study was designed to investigate the effect of glyceryl trinitrate (GTN) and calcium antagonists on ET-1 contraction in the human IMA. 2 Human IMA segments taken from 21 patients undergoing IMA-coronary artery bypass grafting were mounted in an organ bath under the physiological pressure determined from their own length-tension curves. Four ring segments were allocated into four groups. One served as a control and the others were treated with GTN (10, 100 nM, or 30 mu M) for 5 min or nifedipine (20 or 200 nM, or 30 mu M) for 25 min before concentration-contraction curves to ET-1 were established. In separate experiments, the concentration-relaxation Curves to GTN or nifedipine were established in the IMA rings precontracted with ET-1 (10 nM). 3 Pretreatment of IMA with GTN for 5 min did not alter the ET-1-induced contraction. Pretreatment with 20 or 200 nM of nifedipine slightly but not significantly, altered the maximum contraction induced by ET-1. Higher concentrations (30 mu M) significantly reduced the maximum contraction force (P = 0.008). On the other hand, GTN caused 76.44 +/- 6.35% relaxation in ET-1-precontracted IMA. In con trast, the nifedipine-induced relaxation was difficult to establish due to unsustained contraction to ET-1. 4 These results strongly suggest that in the human IMA ET-1-induced contraction may be partially inhibited by nifedipine and the mechanism of ET-1-induced contraction is only partially related to the activation of dihydropyridine-sensitive voltage dependent calcium channels in this artery. The study also demonstrates that although GTN may significantly but not completely reverse the ET-1-induced contraction it may not significantly inhibit the contraction if applied prior to contraction, possibly due to rapid tolerance. These findings may have important clinical implications in coronary artery bypass surgery.