Effect of a lipoxygenase inhibitor on vasoconstriction in dog lung

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 micrograms 5-HT, 1-5 mumol ACh, and 10-50 micrograms 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 microM NDGA did not change base-line LVR, Ra, or Rv; however, 100 microM NDGA increased base-line LVR (P less than 0.05) without increasing Ra or Rv (P greater than 0.05). Neither 50 or 100 microM NDGA affected the pressor response to 5-HT, ACh, or NE; however, the response to 50 micrograms 5-HT was slightly enhanced. Meclo increased base-line LVR (P less than 0.05) and subsequent addition of 50 microM NDGA did not change LVR (P greater than 0.05) from post-Meclo values. The LVR increase to both 5-HT and ACh was potentiated after Meclo (P less than 0.05) and 50 microM 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 microM NDGA after Meclo diminished the increase to 20 and 50 micrograms NE (P less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)