Different activation of the endothelial L-arginine and cyclooxygenase pathway in the human internal mammary artery and saphenous vein

Abstract

The endothelium releases substances controlling vascular tone and platelet function. We investigated mediators of endothelium-dependent responses in human internal mammary arteries and saphenous veins. The inhibitor of nitric oxide formation, N(G)-monomethyl L-arginine, enhanced the sensitivity to norepinephrine (fivefold) and evoked more pronounced endothelium-dependent contractions in internal mammary arteries (19 ± 6% of 100 mM KCl) than in saphenous veins (2 ± 1%; p < 0.005). In internal mammary arteries, N(G)-monomethyl L-arginine, but not indomethacin, markedly reduced endothelium-dependent relaxations to acetylcholine (from 95 ± 2% to 39 ± 7%; p < 0.005) and prevented those to histamine (78 ± 6% to 4 ± 3%; p < 0.005). In saphenous veins, endothelium-dependent relaxations to acetylcholine were weak (24 ± 11%), while nitric oxide caused comparable relaxations (85 ± 3%) as in internal mammary arteries (80 ± 5%; NS). N(G)-Monomethyl L-arginine prevented the relaxations to acetylcholine and unmasked endothelium-dependent contractions (30 ± 10%). Indomethacin and the thromboxane synthetase inhibitor CGS-13080 augmented relaxations of saphenous veins to acetylcholine from 24 ± 11% to 46 ± 9% (p < 0.05). Histamine-evoked contractions were converted to endothelium-dependent relaxations by indomethacin and the thromboxane A2/endoperoxide receptor antagonist SQ-30741 (38 ± 3% and 40 ± 6%; p < 0.05) but not CGS-13080. Thus, 1) nitric oxide mediates endothelium-dependent relaxations in human arteries and veins; 2) internal mammary arteries release more nitric oxide than do saphenous veins, and 3) in saphenous veins, the effects of nitric oxide are reduced by endothelium-derived contracting factors originating from the cyclooxygenase pathway.