NITRIC-OXIDE MODULATION OF PULMONARY VASCULAR-RESISTANCE IS RED-BLOOD-CELL DEPENDENT IN ISOLATED RAT LUNGS

Nitric oxide (NO) or endothelium-derived relaxing factor may play an i mportant role in modulating pulmonary vascular resistance (PVR), altho ugh previous studies have produced conflicting results. Endogenous NO inhibition causes an increase in PVR in intact animals but not in sali ne-perfused isolated lungs. We hypothesized that blood is essential fo r NO to serve as a modulator of PVR. Therefore, the effects of endogen ous NO inhibition (N-omega-nitro-L-arginine methyl ester [L-NAME]) wer e determined in isolated rat lungs as related to the presence of diffe rent blood components under normoxic conditions and after 1 wk of hypo xia (fraction of inspired oxygen [FIO2] = 10%). Exogenously administer ed inhaled NO was evaluated in isolated lungs from normoxic and hypoxi c rats. In normoxic rats, L-NAME (10-100 mu M) caused a dose-dependent increase in PVR in whole (hematocrit [Hct] 40%) and diluted (Hct 12%) blood-perfused lungs. L-NAME (10-800 mu M) had no effect in isolated lungs perfused with a modified salt solution of equal viscosity to blo od either alone, or containing plasma (50%) or free oxyhemoglobin (10 mu M). In whole blood perfused lungs, L-NAME (100 mu M) increased PVR more in hypoxic versus normoxic isolated lungs (141% vs 100%). Inhaled NO decreased PVR in isolated lungs from hypoxic rats and partially re versed the effects of L-NAME, but had no effect in normoxic lungs. In conclusion, endogenous and inhaled NO modulate PVR in isolated rat lun gs and this role is increased by prolonged hypoxia. The response to in hibition of endogenous NO is dependent on the presence of red blood ce lls and is independent of the changes in viscosity or the presence of oxyhemoglobin or plasma.