BACKGROUND: Graft spasm in the internal mammary artery (IMA) may occur after coronary artery bypass grafting (CABG). We investigated the effect of human urotensin II (hU-II), a cyclic peptide hormone present in human blood and tissues, and the effect of vasodilators on hU-II-mediated response in human IMA. METHODS: Fresh IMA segments (n=114) taken from 50 patients undergoing CABG were studied in a myograph. The interaction between hU-II and various calcium antagonists or glyceryl trinitrate (GTN) was investigated in 2 ways: relaxing effect of vasodilators on the hU-II-induced precontraction and depressing effect of vasodilator agents on the contraction caused by hU-II (n=6 to 10 in each subgroup). RESULTS: Human urotensin II caused contractile response in all human IMA. In potassium chloride-contraction, full (nifedipine: 99.1 %±2.7%) or nearly full (diltiazem: 93.5%±4.8%) relaxation with 30.9-fold higher potency to nifedipine than to diltiazem (EC50 [effective concentration causing 50% of maximal response] -8.24±0.21 vs -6.75±0.20 log M, p=0.0002) and in hU-II-contraction, nearly full relaxation (nifedipine: 90.6%±4.6%; diltiazem: 95.0%±1.7%) with 5.8-fold higher potency to nifedipine than to diltiazem (EC50 -7.55±0.26 vs -6.79±0.25 log M, p=0.03) were observed. The GTN caused nearly full relaxation (93.1%±4.8%) but GTN pretreatment had limited effect in prevention of the hU-II-induced contraction, whereas diltiazem and nifedipine reduced subsequent contraction to hU-II. CONCLUSIONS: Human urotensin II is a potent vasoconstrictor in human IMA. Calcium antagonists and GTN relax the contraction caused by hU-II with different potencies. However, calcium antagonists are more effective than GTN in preventing the contraction induced by hU-II. These findings may have clinical implications in CABG.
BACKGROUND: Graft spasm in the internal mammary artery (IMA) may occur after coronary artery bypass grafting (CABG). We investigated the effect of humanurotensin II (hU-II), a cyclic peptide hormone present in human blood and tissues, and the effect of vasodilators on hU-II-mediated response in human IMA. METHODS: Fresh IMA segments (n=114) taken from 50 patients undergoing CABG were studied in a myograph. The interaction between hU-II and various calcium antagonists or glyceryl trinitrate (GTN) was investigated in 2 ways: relaxing effect of vasodilators on the hU-II-induced precontraction and depressing effect of vasodilator agents on the contraction caused by hU-II (n=6 to 10 in each subgroup). RESULTS:Humanurotensin II caused contractile response in all human IMA. In potassium chloride-contraction, full (nifedipine: 99.1 %±2.7%) or nearly full (diltiazem: 93.5%±4.8%) relaxation with 30.9-fold higher potency to nifedipine than to diltiazem (EC50 [effective concentration causing 50% of maximal response] -8.24±0.21 vs -6.75±0.20 log M, p=0.0002) and in hU-II-contraction, nearly full relaxation (nifedipine: 90.6%±4.6%; diltiazem: 95.0%±1.7%) with 5.8-fold higher potency to nifedipine than to diltiazem (EC50 -7.55±0.26 vs -6.79±0.25 log M, p=0.03) were observed. The GTN caused nearly full relaxation (93.1%±4.8%) but GTN pretreatment had limited effect in prevention of the hU-II-induced contraction, whereas diltiazem and nifedipine reduced subsequent contraction to hU-II. CONCLUSIONS:Humanurotensin II is a potent vasoconstrictor in human IMA. Calcium antagonists and GTN relax the contraction caused by hU-II with different potencies. However, calcium antagonists are more effective than GTN in preventing the contraction induced by hU-II. These findings may have clinical implications in CABG.