Contraction and Relaxation Responses to fMLP in Isolated Human Coronary Arteries

Abstract

The intimal thickening commonly found in human coronary arteries involves macrophage infiltration; this may contribute to the development of local vascular tone. We investigated the effects of the leukocyte stimulant, N-formyl-L-methionyl- L-leucyl-L-phenylalanine (fMLP), on human coronary arterial tone. For isometric tension recording, isolated human coronary arterial rings were suspended in a tissue bath filled with Krebs-Ringer solution. A single dose of fMLP (10⁻⁵M) was added to rings precontracted with 10⁻⁵M phenylephrine. Tension changes in response to fMLP were expressed as percentages of maximum potassium contraction or maximum papaverine relaxation. The inhibitors used were pretreated 15min before the addition of phenylephrine. In parallel, coronary segments were histologically examined for identifying the infiltrated inflammatory cells. In most cases examined, fMLP at 10⁻⁵M produced biphasic tension changes, with rapid contraction followed by relaxation (60±9%/–52±10%). Removal of the endothelium or adventitia did not alter the responses to fMLP. The contraction phase was nearly abolished by the thromboxane A₂/prostaglandin H₂ (TXA₂/PGH₂) receptor blocker, ONO3708 (10⁻⁶M; 0%/–72±12%), and the selective TXA₂ synthetase inhibitor, DP-1904 (10⁻⁵M; 11 ±4%/–55± 11 %). Indomethacin (2 × 10⁻⁵M) inhibited both phases, but the contraction remained small (11 ± 4%). However, the selective PGI₂ synthetase inhibitor tranylcypromine (10⁻⁴M) did not reduce the relaxation phase in the presence of ONO3708 (−49 ± 15%).