Inhibition of nitric oxide synthesis augments pulmonary oedema in isolatedperfused rabbit lung

The role of nitric oxide (NO) in precipitating pulmonary oedema in acute lu ng injury remains unclear. We have investigated the mechanism of involvemen t of NO in the maintenance of liquid balance in the isolated rabbit lung. T hirty pairs of lungs were perfused with colloid for up to 6 h, during which pulmonary vascular resistance (PVR) and capillary pressure (PCP) were meas ured frequently, and time to gain 5 g in weight (t(5)) was recorded. Four p rotocols with different perfusate additives were studied: (i) none (control , n=11); (ii) 10 mmol N-G-nitro-L-arginine methyl ester (L-NAME) (n=6); (ii i) 10 mmol L-NAME with 100 mu mol lodoxamide, an inhibitor of mast cell deg ranulation (n=7); (iv) 10 mmol L-NAME with 10 mu mol 8-bromo-3',5'-cyclic g uanosine monophosphate (8Br-cGMP), an analogue of cGMP that may reduce vasc ular permeability by relaxing contractile elements in endothelial cells (n= 6). Neither PVR nor PCP differed between protocols. L-NAME markedly reduced g from 248 (27) min (mean (SEM)) in protocol (i) to 144 (5) min in protoco l (ii) (P<0.05). Both lodoxamide (t(5)=178 (7) min) and 8Br-cGMP (t(5)=204 (10) min) substantially corrected the effect of L-NAME (P<0.005). Results s uggest that maintenance of a low permeability by NO may involve mast cell s tabilization and endothelial cell relaxation.