Mechanisms of L-NG nitroarginine/indomethacin-resistant relaxation in bovine and porcine coronary arteries.
1. Coronary arteries from bovines (BCA) and pigs (PCA) were used for measuring endothelium-dependent relaxation in the presence of L-NG nitroarginine and indomethacin. As some compounds tested have been found to have an inhibitory effect on autacoid-activated endothelial Ca2+ signalling, endothelium-dependent relaxation was initiated with the Ca2+ ionophore A23187. 2. The common compounds for modulating arachidonic acid release/pathway, mepacrine and econazole only inhibited L-NG nitroarginine-resistant relaxation in BCA not in PCA. In contrast, proadifen (SKF 525A) diminished relaxation in BCA and PCA. Mepacrine and proadifen inhibited Hoe-234-initiated relaxation in BCA and PCA, while econazole only inhibited Hoe 234-induced relaxation in PCA. Due to the multiple effects of these compounds, caution is necessary in the interpretation of results obtained with these compounds. 3. The inhibitor of Ca(2+)-activated K+ channels, apamin, strongly attenuated A23187-induced L-NG nitroarginine-resistant relaxation in BCA while apamin did not affect L-NG nitroarginine-resistant relaxation in PCA. 4. Pertussis toxin blunted L-NG nitroarginine-resistant relaxation in BCA, while relaxation of PCA was not affected by pertussis toxin. 5. Thiopentone sodium inhibited endothelial cytochrome P450 epoxygenase (EPO) in PCA but not in BCA, while L-NG nitroarginine-resistant relaxation of BCA and PCA were unchanged. Protoporphyrine IX inhibited EPO in BCA and PCA and abolished L-NG nitroarginine-resistant relaxation of BCA not PCA. 6. An EPO-derived compound, 11,12-epoxy-eicosatrienoic acid (11,12-EET) yielded significant relaxation in BCA and PCA in three out of six experiments. 7. These findings suggest that L-NG nitroarginine-resistant relaxation in BCA and PCA constitutes two distinct pathways. In BCA, activation of Ca(2+)-activated K+ channels via a pertussis-toxin-sensitive G protein and EPO-derived compounds might be involved. In PCA, no selective inhibition of L-NG nitroarginine-resistant relaxation was found.
Graier
W F
WF
Department of Medical Biochemistry, University of Graz, Austria.
Holzmann
S
S
Hoebel
B G
BG
Kukovetz
W R
WR
Kostner
G M
GM
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000187:drug effects; D011524:Protoporphyrins / Q000494:pharmacology; D013552:Swine; D013874:Thiopental / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015221:Potassium Channels; D011524:Protoporphyrins; D010566:Virulence Factors, Bordetella; D019335:Nitroarginine; D001030:Apamin; D000001:Calcimycin; D010042:Ouabain; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; D003577:Cytochrome P-450 Enzyme System; C028025:protoporphyrin IX; D037342:Pertussis Toxin; D015126:8,11,14-Eicosatrienoic Acid; D013874:Thiopental; D007213:Indomethacin