INCREASED EFFICIENCY TO ANGIOTENSIN II INDUCED BY SIMULTANEOUS INHIBITION OF EPOXYGENASE AND OMEGA HYDROXYLASE

SIERRA L; SCACHI FABRICIO; PERAL DE BRUNO M,; JEREZ S

Tandil Bs As

Congreso; XL REUNION ANUAL SAFE; 2008

Sociedad Argentina de farmacologia experimental

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> This study was designed to analyze the mechanims of contractile response increase to Angiotensin II (Ang II) in presence of 17-Octadecynoic acid (17­-ODYA). Thoracic aorta from rabbits was excised. Rings were cut and mounted in an organ bath to register isometric contractions in arteries with endothelium. Arteries were incubated or not (control) with 17-ODYA, 17-ODYA+Indomethacin, NS398, SQ 29548, 17ODYA + NS398 o SQ 29548, Miconazol, CAY 10434 y Miconazol+CAY10434 and stimulated with NA and one CDRC (cumulative dose-response curve) to Ach. After washing, one CDRC to Ang II was performed. 17-ODYA increased maximal response (Emax) to Ang II and disminished Ach-relaxation. Arteries treated with 17-ODYA plus indomethacin, NS398 or SQ29548 induced a shift to the right to AngII-CDRC. However, only indomethacin and NS398 blocked Emax-increase.  Miconazol increased affinity but not Emax. CAY10434 did not modify Ang II response. Furthermore, Miconazol+CAY10434 induced AngII- Emax increase similar to 17-ODYA. Simultaneously inhibition of epoxygenase and hidroxylase induced release of COX-dependent metabolite which increased efficiency and potency to Ang II. This metabolite modulates Ang II potency through TXA2/PGH2 receptors. EETs but not 20-HETE would modify Ang II affinity in physiological conditions.