title: Leukotriene D4 potentiates the contractile effects of epinephrine and norepinephrine on rat aortic rings.
abstract: Previous studies have demonstrated a cooperative interaction between peptido-leukotrienes (LTs) and epinephrine (EPI) relative to induction of platelet aggregation and thromboxane formation. To examine if a similar interaction occurs in arteries, we studied the effects of LTD4 and EPI as well as norepinephrine (NOREPI) on isolated rat aortic rings. LTD4 alone (mean concentration 2 x 10(-7) M) induced contraction in 10 of 15 rings examined (mean peak tension 0.31 +/- 0.27 g/mg of tissue). However, pretreatment of aortic rings with LTD4 (10(-7) M) consistently and significantly enhanced the contractile effects of EPI and NOREPI and lowered the threshold concentration of these agonists required to evoke contraction from 4 x 10(-9) to 3 x 10(-10) M (P less than .05). This enhancement of the sensitivity of aortic rings by LTD4 was not observed when KCl or 5-hydroxytryptamine was used as agonists. Furthermore, the LTD4-induced potentiation of effects of EPI or NOREPI on aortic contraction was blocked by the LT-receptor antagonist FPL-55712, but not by indomethacin. These data suggest a specific cooperative contractile effect of LTD4 and alpha adrenergic agonists on rat aortic rings. This LTD4 potentiation of vascular contraction is mediated through LT-receptor stimulation and not through release of cyclooxygenase metabolites.
authors.affiliation: Veterans Administration Medical Center, Gainesville, Florida.
authors.forename: D L
authors.initials: DL
authors.lastname: Lawson
authors.forename: C
authors.initials: C
authors.lastname: Smith
authors.forename: J L
authors.initials: JL
authors.lastname: Mehta
authors.forename: P
authors.initials: P
authors.lastname: Mehta
authors.forename: W W
authors.initials: WW
authors.lastname: Nichols
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D004285:Dogs; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D066298:In Vitro Techniques; D017999:Leukotriene E4; D009638:Norepinephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000031:analogs & derivatives / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D013189:SRS-A; D012701:Serotonin; D011189:Potassium Chloride; D017999:Leukotriene E4; D009638:Norepinephrine; D004837:Epinephrine