The interaction between human urotensin II and vasodilator agents in human internal mammary artery with possible clinical implications.

Abstract

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. 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). 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. 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.