CONICET | Buscador de Institutos y Recursos Humanos

17-Octadecynoic acid improves contractile response to angiotensin II by releasing vasocontrictor prostaglandins. Jerez S, Sierra L, Peral de Bruno M. Laboratorio de Fisiologia y Farmacologia Vascular, Departamento de Bioingeniería, Instituto Superior de Investigaciones Biológicas (UNT - CONICET)-Facultad de Ciencias Naturales e Instituto Miguel Lillo. Abstract 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. Copyright © 2011 Elsevier Inc. All rights reserved.

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