MECHANISMS OF L-N-G NITROARGININE INDOMETHACIN-RESISTANT RELAXATION IN BOVINE AND PORCINE CORONARY-ARTERIES/

1 Coronary arteries from bovines (BCA) and pigs (PCA) were used for me asuring endothelium-dependent relaxation in the presence of L-N-G nitr oarginine and indomethacin. As some compounds tested have been found t o have an inhibitory effect on autacoid-activated endothelial Ca2+ sig nalling, endothelium-dependent relaxation was initiated with the Ca2ionophore A23187. 2 The common compounds for modulating arachidonic ac id release/pathway, mepacrine and econazole only inhibited L-N-G nitro arginine-resistant relaxation in BCA not in PCA. In contrast, proadife n (SKF 525A) diminished relaxation in BCA and PCA. Mepacrine and proad ifen inhibited Hoe-234-initiated relaxation in BCA and PCA, while econ azole only inhibited Hoe 234-induced relaxation in PCA. Due to the mul tiple effects of these compounds, caution is necessary in the interpre tation of results obtained with these compounds. 3 The inhibitor of Ca 2+-activated K+ channels, apamin, strongly attenuated A23187-induced L -N-G nitroarginine-resistant relaxation in BCA while apamin did not af fect L-N-G nitroarginine-resistant relaxation in PCA. 4 Pertussis toxi n blunted L-N-G nitroarginine-resistant relaxation in BCA, while relax ation of PCA was not affected by pertussis toxin. 5 Thiopentone sodium inhibited endothelial cytochrome P450 epoxygenase (EPO) in PCA but no t in BCA, while L-N-G nitroarginine-resistant relaxation of BCA and PC A were unchanged. Protoporphyrine IX inhibited EPO in BCA and PCA and abolished L-N-G nitroarginine-resistant relaxation of BCA not PCA. 6 A n EPO-derived compound, 11,12-epoxy-eicosatrienoic acid (11,12-EET) yi elded significant relaxation in BCA and PCA in three out of six experi ments. 7 These findings suggest that L-N-G nitroarginine-resistant rel axation in BCA and PCA constitutes two distinct pathways. In BCA, acti vation of Ca2+-activated K+ channels via a pertussis-toxin-sensitive G protein and EPO-derived compounds might be involved. In PCA, no selec tive inhibition of L-N-G nitroarginine-resistant relaxation was found.