Inhibitory effects of calcium antagonists on alpha‐adrenoceptor‐ mediated contraction in the human internal mammary artery.

Abstract

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 alpha 1‐adrenoceptor agonist methoxamine (MO) or full alpha‐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 microM) or NA (10 microM). Glyceryl trinitrate (GTN, 3 microM) 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.(ABSTRACT TRUNCATED AT 250 WORDS) 1994 The British Pharmacological Society