INHIBITORY EFFECTS OF CALCIUM-ANTAGONISTS ON ALPHA-ADRENOCEPTOR-MEDIATED CONTRACTION IN THE HUMAN INTERNAL MAMMARY ARTERY

1 The internal mammary artery has become a preferred coronary bypass graft. Sympathomimetic amines are spasmogens for vasospasm and calcium antagonists are frequently administered drugs perioperatively. The effect of calcium antagonists on alpha-adrenoceptor-mediated contraction depends on the subtype of alpha-adrenoceptor and the type of origin of vascular smooth muscle. This study was designed to investigate the effect of calcium antagonists on alpha-adrenoceptor-mediated contraction in the IMA. 2 Human IMA segments taken from 22 patients undergoing IMA - coronary artery bypass grafting were mounted in an organ bath under the physiological pressure determined from their own length-tension curves. 3 Three ring segments were allocated into three groups. One served as a control and the others were treated with clinically related concentrations of nifedipine (20 or 200 nM) for 25 min before concentration-contraction curves to al-adrenoceptor agonist methoxamine (MO) or full cr-adrenoceptor agonist noradrenaline (NA) were established. 4 In separate experiments, the concentration-relaxation curves to nifedipine were established in the IMA rings precontracted with MO (30 mu M) or NA (10 mu M). Glyceryl trinitrate (GTN, 3 mu M) was added to further relax the vessels. 5 Pretreatment with nifedipine (200 nM) only slightly inhibited the MO- (1.74 +/- 0.32 vs 2.88 +/- 0.56 g) or NA- (2.43 +/- 0.66 vs 3.60 +/- 0.82 g) induced contraction without statistical significance (P > 0.05). 6 On the other hand, nifedipine only caused 34.49% relaxation in the MO-precontracted and 24.39% relaxation in the NA-precontracted IMAs. In contrast, GTN caused 76.16% (against MO, P < 0.05) or 92.22% (against NA, P < 0.0001) relaxation. 7 These results strongly suggest that the inhibitory effect of nifedipine on adrenoceptor-mediated contraction in the IMA is limited due to the incomplete inhibition through the alpha(1)-mechanism. Therefore, calcium antagonists may be ineffective in treating sympathomimetic amine-induced IMA spasm.