17-Octadecynoic acid improves contractile response to angiotensin II by releasing vasocontrictor prostaglandins

[Display omitted] ► 17-Octadecynoic acid increases response to angiotensin II in rabbit aortae. ► Endothelium-dependent and -independent mechanisms are involved in the 17-ODYA-effect. ► Simultaneously inhibition of epoxygenase and ω-hydroxylase increases angiotensin II-response. ► Epoxygenase- inhibition improves endothelium-dependent vasoconstrictor COX-2 metabolites-release. ► Prostaglandin-ω-hydroxylase-inhibition improves COX-metabolites release from smooth muscle. The present study investigated the role of CYP-enzymes in the modulation of vasoconstrictor responses to angiotensin II in rabbit aortae. In arteries with the endothelium-intact ( E+) the CYP-inhibitor, 17-octadecynoic acid (17 ODYA), increased the efficacy to angiotensin II (17-ODYA-effect) as well as simultaneous incubation with miconazole (epoxygenase-inhibitor) and CAY 10434 (ω-hydroxylase-inhibitor). The removal of endothelium ( E−) caused potentiation of the 17 ODYA-effect. Therefore, endothelium-dependent and -independent mechanisms would be involved. 17-ODYA and miconazole reduced Ach-relaxation. Indomethacin blocked the 17-ODYA-effect in E+ and E− arteries but blunted the response to angiotensin II only in E+ arteries. NS 398 (cyclooxygenase-2-inhibitor) blocked the 17-ODYA-effect and reduced angiotensin II affinity as well as SQ 29548 (thromboxane-prostanoid (TP) receptor-inhibitor). In E− arteries, CAY 10434 enhanced angiotensin II response as well as 17-ODYA. SC 560 (cyclooxygenase-1-inhibitor) and NS 398 partially blocked the 17-ODYA-effect. In conclusion, 17-ODYA induced endothelial dysfunction by inhibiting CYP-epoxygenase and thus improves vasoconstrictor cyclooxygenase-2 metabolites release acting through TP receptors. The endothelium-independent mechanism of 17-ODYA-effect may involve increase of vasoconstrictor cyclooxygenase-metabolites induced by prostaglandin-ω-hydroxylase-inhibition.