Leukotriene biosynthesis by canine and human coronary arteries

Canine and human epicardial coronary arteries were tested for their ability to metabolize exogenous arachidonic acid to lipoxygenase products. Unextracted medium from incubations of canine or human arteries with arachidonic acid and the calcium ionophore, A23187, contained a substance which exhibited a leukotriene (LT)-like smooth muscle contracting activity when tested on the superfused guinea pig lung parenchymal strip bioassay. This activity could be blocked by the LT antagonist, FPL-55712. Compounds present in these media were purified by high-performance liquid chromatography and identified as LTC4, LTD4 and LTE4 by liquid scintillation counting, bioassay and radioimmunoassay. In addition, coronary artery rings converted synthetic [3H]LTC4 to [3H]LTD4 with a half-life of 44 +/- 8 min. LTD4 metabolism to LTE4 was also demonstrated. The metabolism of [3H]LTC4 was abolished by incubation of the arterial rings with a gamma-glutamyl transpeptidase inhibitor, serineborate. Production of monohydroxyeicosatetraenoic acids (5-, 12- and 15-HETE) which have been isolated previously from vascular tissue incubations was confirmed. Production of HETE was inhibited by nordihydroguaiaretic acid and unaffected by indomethacin. These findings indicate that coronary vessels can metabolize exogenous arachidonic acid by the lipoxygenase pathway. In addition to HETE, the vessels were shown to synthesize LTC4, LTD4 and LTE4, compounds which possess potent biological actions on the coronary circulation.