title: 17-Octadecynoic acid improves contractile response to angiotensin II by releasing vasocontrictor prostaglandins.
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.
authors.affiliation: Laboratorio de Fisiologia y Farmacologia Vascular, Departamento de Bioingeniería, Instituto Superior de Investigaciones Biológicas (UNT - CONICET), Universidad Nacional de Tucumán, Tucumán, Argentina. sjerez@herrera.unt.edu.ar
authors.forename: Susana
authors.initials: S
authors.lastname: Jerez
authors.forename: Liliana
authors.initials: L
authors.lastname: Sierra
authors.forename: María Peral
authors.initials: MP
authors.lastname: de Bruno
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008825:Miconazole / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D016861:Cyclooxygenase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D011453:Prostaglandins; D000804:Angiotensin II; D009599:Nitroprusside; D009569:Nitric Oxide; C047008:17-octadecynoic acid; D011189:Potassium Chloride; D008825:Miconazole; D011451:Prostaglandin-Endoperoxide Synthases; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine