HUMAN PULMONARY-ARTERIES DILATE TO 20-HETE, AN ENDOGENOUS EICOSANOID OF LUNG-TISSUE

We investigated the effect of 20-hydroxyeicosatetraenoic acid (SO-HETE ), an arachidonic acid metabolite of the cytochrome P-450 (cP450) 4A p athway, on human pulmonary arterial tone. 80-HETE elicited a dose-depe ndent and indomethacin-inhibitable vasodilation of isolated small pulm onary arteries. Whole lung microsomes metabolized [C-14]arachidonic ac id into SO-HETE and a variety of leukotrienes, epoxyeicosatrienoic aci ds, and prostanoids. Indomethacin blocked formation of prostanoids wit hout effects on the conversion of arachidonate into 20-HETE. 80-HETE w as converted by lung microsomes into prostanoids, raising the possibil ity that 20-HETE may be metabolized by cyclooxygenase enzymes in vascu lar tissue to a vasodilatory compound. Western blots probed with a pol yclonal antibody to cP450 4A identified a protein of similar to 50 kDa immunologically similar to the cP450 4A in rat liver. We conclude tha t small arteries from human lungs dilate upon exposure to 80-HETE in a cyclooxygenase-dependent manner and that the proteins and enzymatic a ctivity required to synthesize this product are present in lungs. Our observations suggest that cP450 enzyme products could be endogenous mo dulators of pulmonary vascular tone.