Effect of a lipoxygenase inhibitor on vasoconstriction in dog lung
el-Kashef, H.A.; Hofman, W.F.; Ehrhart, I.C.
American Journal of Physiology 257(6 Pt 2): H1977-H1982
1989
ISSN/ISBN: 0002-9513 PMID: 2513733 Document Number: 342842
The effects of lipoxygenase inhibition and cyclooxygenase plus lipoxygenase inhibition on the pressor responses to serotonin (5-HT), acetylcholine (ACh), and norepinephrine (NE) were studied in the isolated, blood-perfused dog lung. Bolus doses of 50-250 .mu.g 5-HT, 1-5 .mu.mol ACh, and 10-50 .mu.g NE were given before and after the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), or the cyclooxygenase inhibitor, meclofenemate (Meclo), followed by NDGA. Lobar vascular resistance (LVR) was partitioned into upstream (Ra) and downstream (Rv) segments by venous occlusion. 50 .mu.M NDGA did not change base-line LVR, Ra, or Rv; however, 100 .mu.M NDGA increased base-line LVR (P < 0.05) without increasing Ra or Rv (P > 0.05). Neither 50 or 100 .mu.M NDGA affected the pressor response to 5-HT, ACh, or NE; however, the response to 50 .mu.g 5-HT was slightly enhanced. Meclo increased base-line LVR (P < 0.05) and subsequent addition of 50 .mu.M NDGA did not change LVR (P > 0.05) from post-Meclo values. The LVR increase to both 5-HT and ACh was potentiated after Meclo (P < 0.05) and 50 .mu.M NDGA after Meclo did not change the LVR increase to either 5-HT or ACh. In contrast, Meclo did not enhance the pressor response to NE, and addition of 50 .mu.M NDGA after Meclo diminished the increase to 20 and 50 .mu.g NE (P < 0.05). Our results suggest that unlike cyclooxygenase inhibition, lipoxygenase inhibition does not increase base-line LVR or the pressor response to either 5-HT or ACh. Thus the enhanced vasopressor response to 5-HT and ACh after Meclo does not appear related to a shift of arachidonic acid metabolism toward the lipoxygenase pathway. However, the pressor response to NE may be dependent on the release of vasoconstrictor lipoxygenase products.