Leukotriene D4 potentiates the contractile effects of epinephrine and norepinephrine on rat aortic rings

DL Lawson, C Smith, JL Mehta, P Mehta and WW Nichols

Veterans Administration Medical Center, Gainesville, Florida.

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.

Volume 247, Issue 3, pp. 953-957, 12/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics

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