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1. Endothelium-dependent relaxant responses and modulation of contractile responses were investigated in human isolated internal mammary artery (HIMA), a vessel widely used for coronary bypass surgery. 2. Acetylcholine and ionophore A23187 (both 10 nM-1 microM) elicited concentration-dependent relaxations of precontracted HIMA. These relaxations were abolished after rubbing of the endothelium, they were inhibited by methylene blue and were insensitive to indomethacin. 3. Histamine at concentrations lower than 10 microM elicited an endothelium-dependent, methylene blue-sensitive relaxation of precontracted HIMA. This effect of histamine was inhibited by the H1-receptor antagonist mepyramine. Bradykinin, noradrenaline and alpha 2-adrenoceptor agonists (in the presence of prazosin) did not relax unrubbed HIMA in which acetylcholine or A23187 were shown to be efficient. 4. Tissue levels of guanosine-3':5'-monophosphate (cyclic GMP) were found to be significantly higher in unrubbed HIMA rings than in matched rubbed rings. 5. Methylene blue evoked a slow contraction in resting HIMA, and this contraction was significantly greater in unrubbed than in rubbed preparations. Also, methylene blue enhanced the contractile response of HIMA to noradrenaline and this potentiating effect was significantly greater in unrubbed than in rubbed preparations. Indomethacin induced a slow contraction, of similar magnitude in unrubbed and rubbed HIMA rings. 6. In resting HIMA, the concentration-effect curve of noradrenaline-induced contraction was significantly shifted to the left after rubbing of the endothelium, without change in the maximal responses. In unrubbed rings the EC50 value of noradrenaline was about 2 fold that in rubbed rings. 7. Histamine also contracted resting HIMA in a concentration-dependent manner and in addition, it triggered rhythmic activity. This rhythmic activity was more prominent in unrubbed preparations and could be partially inhibited by indomethacin. The concentration-effect curve of histamine-induced contractions was displaced to the left after rubbing the endothelium, without changes in the maximal responses. The EC50 value of histamine in unrubbed rings was 4 to 9 fold that found in rubbed rings, depending on the level of tension taken into account for the concentration-effect curve during rhythmic contractions. 8. In the presence of nifedipine (3 microM), noradrenaline-induced contractions were not significantly altered, whereas histamine-induced contractions were found to be inhibited by about 70%. 9. It is concluded that in HIMA, both spontaneous and stimulated endothelium-dependent relaxing factor (EDRF) release may occur, and that basal EDRF can itself be responsible for the modulatory effect of endothelium on contractile responses.
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