CONTRACTION OF GUINEA-PIG INFERIOR VENA-CAVA BY EICOSANOIDS

Guinea pig inferior vena cava contracted in response to leukotriene (L T)C4, LTD4, LTE4 U46619, phenylephrine, histamine, and KCl. Although L TC4, LTD4, and U46619 were the most potent agonists, active tension ge nerated by these eicosanoids was only about half that of histamine or KCl. LTE4 and phenylephrine were marginally active. Biochemical analys is showed vena cava able to convert about 23% LTC4 to LTD4 and LTE4 in 45 min. Pretreatment with acivicin prevented this by abrogating conve rsion of LTC4 to LTD4. A subthreshold concentration of LTE4 reduced re sponses to LTC4 and LTD4. LY171883 and WY-48252 competitively antagoni zed LTD4-induced contractions of vena cava. In contrast, these antagon ists blocked contractions to LTC4 in a biphasic manner. Lower segments of the LTC4 concentration-response curves were less affected than the upper portion suggesting the possibility of 2 LTC4 receptor subtypes. Our results indicate that LTE4 is a weak or partial agonist in this t issue and furthermore they suggest a lack of high affinity receptors f or LTE4 favoring LTC4 and LTD4. Indomethacin did not influence contrac tions to the leukotrienes or histamine. However, the response to U4661 9 was greatly enhanced suggesting release of a vasodilator prostagland in as part of the overall response of the vena cava to the thromboxane A2 mimetic.