LEUKOTRIENE METABOLISM BY INTRAPULMONARY VESSELS OF NEWBORN LAMBS: Effect of Platelet-Activating Factor

Abstract

Leu kotrien es (LTs ) are poten t v asocon strictors in the pu lmon ary circu lation . We in v estigated LTB 4 an d LTE 4 metabolism by in trapu lmon ary arteries an d v ein s of 2 to 9 days old lambs . n H 6 ).Paired v essels were in cu bated u n der baselin e, an d stimu lated con dition s. LTB 4 an d LTE 4 were extracted from media, qu an ti ed by en zyme-lin ked immu n osorben t assay (ELISA ), n ormalized to tissu e weig ht an d presen ted as n g /mg tissu e (mean s SEMs ). In arteries, baselin e syn thesis of LTB 4 was 0.15 0.20 an d in creased to 0.96 0.04 on stimu lation with 1.0 mol/L A2318, an d 1.74 0.25 with 0.1 mmol/L arachidon ic acid (AA ). In v ein s the correspon din g v alu es were 0.28 0.10, 2.50 0.51, an d 5.36 0.70. Baselin e produ ction of LTB 4 was hig her in v ein s. LTE 4 syn thesis in arteries was 0.25 0.02, which in creased to 0.42 0.05 with A23187, an d fu rther to 0.69 0.06 with AA. The correspon din g v alu es in v ein s were 0.23 0.05, 0.74 0.09, an d 1.56 0. Baselin e metabolism of LTE 4 by the v essels was n ot differen t. Fu rthermore, stimu lation of v essels with 50 n mol/L PAF led to ov er 3-fold in crease in LTB 4 an d LTE 4 metabolism by the v essels. Smooth mu scle cells stimu lated with A23187 metabolized LTB 4 an d LTC 4 , which was sequ en tially catabolized to LTD 4 an d LTE 4 .Gen erally, stimu lated v ein s, whether v essels or sm ooth mu scle cells, metabolized more leu kotrien es. The selectiv e 5-lipoxygen ase in hibitor, AA-861, sign i can tly atten u ated syn thesis of both leu kotrien es. Western an alysis of membran e protein showed greater expression of 5-lipoxygen ase in stimu lated v ein s. Ou r data sh ow that v ein s produ ce more leu kotrien es du e to greater expression of 5-lipoxyg en ase in the v essels, an d su g gest that v ein s of n ewborn lamb lu n gs may be more su sceptible to LT-in du ced v ascu lar reactiv ity in the pu lmon ary circu lation .