Fundamental Differences in Actions of Arachidonate Mediators and NO in the Pulmonary Circulation

Abstract

We are interested in the actions of arachidonic acid and NO mediators on the pulmonary circulation. AA mediators can directly cause vasoconstriction or dilatation and peptide leukotrienes can directly cause increased permeability. There appear to be tonic production of prostacyclin and NO in the pulmonary circulation (Am Rev Resp Dis 137:1343–1349, 1988) although it is not known if either is necessary for low perfusion pressure. To study the actions of EDRF-NO in the pulmonary circulation, we administered the NO-synthase inhibitor, N-Nitro-L-Arginine (NLA) to a well characterized isolated lung preparation (ibid) perfused with K-H buffer. At a perfusate concentration of 150uM, NLA caused pulmonary hypertension and edema formation. An index of capillary filtration coefficient was significantly increased. These changes could be prevented with pretreatment with 300uM L-Arginine or a combination of pretreatment and treatment with 8-bromo-cAMP. Although we did not study L-Arginine in arachidonate lung injury, 8-bromo-cAMP did not ameliorate lung injury as measured by capillary filtration coefficient. In keeping with a fundamental different mechanism of injury, cAMP did not ameliorate NLA lung injury but is very effective in inhibiting AA mediator induced oxidant lung injury.