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

• Published in: Prostaglandins & other lipid mediators Vol. 97; no. 1; pp. 36 - 42
• Main Authors: Jerez, Susana, Sierra, Liliana, Peral de Bruno, María
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2012
• Subjects: 17-Octadecynoic acid; Angiotensin II; Angiotensin II - pharmacology; Animals; Cyclooxygenase; Cyclooxygenase Inhibitors - pharmacology; Cytochrome P 450 inhibition; Cytochrome P-450 Enzyme Inhibitors; Fatty Acids, Unsaturated - pharmacology; In Vitro Techniques; Male; Miconazole - pharmacology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - enzymology; Muscle, Smooth, Vascular - physiology; Muscle, Smooth, Vascular - secretion; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - metabolism; Nitroprusside - pharmacology; Norepinephrine - pharmacology; Potassium Chloride - pharmacology; Prostaglandin-Endoperoxide Synthases - metabolism; Prostaglandins - secretion; Rabbits; Vascular response; Vasoconstriction - drug effects; Cytochrome P 450 inhibition; Cyclooxygenase; 17-Octadecynoic acid; Angiotensin II; Vascular response
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2011.07.008

[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.