Lawson D L, Smith C, Mehta J L, Mehta P, Nichols W W
Veterans Administration Medical Center, Gainesville, Florida.
J Pharmacol Exp Ther. 1988 Dec;247(3):953-7.
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.
先前的研究已经证明，相对于诱导血小板聚集和血栓素形成，肽白三烯（LTs）和肾上腺素（EPI）之间存在协同相互作用。为了研究在动脉中是否发生类似的相互作用，我们研究了白三烯D4（LTD4）、EPI以及去甲肾上腺素（NOREPI）对离体大鼠主动脉环的影响。单独使用LTD4（平均浓度2×10⁻⁷ M）时，在检测的15个主动脉环中有10个出现收缩（平均峰值张力为0.31±0.27 g/mg组织）。然而，用LTD4（10⁻⁷ M）预处理主动脉环可持续且显著增强EPI和NOREPI的收缩作用，并将引发收缩所需的这些激动剂的阈值浓度从4×10⁻⁹ M降低至3×10⁻¹⁰ M（P<0.05）。当使用氯化钾或5-羟色胺作为激动剂时，未观察到LTD4对主动脉环敏感性的这种增强作用。此外，LTD4诱导的EPI或NOREPI对主动脉收缩作用的增强被白三烯受体拮抗剂FPL-55712阻断，但未被吲哚美辛阻断。这些数据表明LTD4与α肾上腺素能激动剂对大鼠主动脉环具有特定的协同收缩作用。LTD4对血管收缩的这种增强作用是通过白三烯受体刺激介导的，而不是通过环氧化酶代谢产物的释放介导的。
