Herne oxygenase does not contribute to control of basal vascular tone in isolated blood-perfused rat lung

Background: Vasoconstriction in pulmonary ischemia-reperfusion injury may involve dysfunction of the physiologic vasodilation of pulmonary arteries. Little is known of the relative importance of heme oxygenase (HO)/carbon monoxide (CO)-dependent vs nitric oxide synthase (NOS)/nitric oxide (NO)-dependent vasodilation of the pulmonary vasculature. We evaluated the significance of HO function on basal pulmonary vascular resistance (PVR) and compared it with the function of NOS. Methods: Using an isolated blood-perfusion model, lungs of Lewis rats were assigned to 3 groups (n = 6/group). After stabilization, either an inhibitor of HO (tin-protoporphyrin-9 [SnPP-9]) or an inhibitor of NOS (NG-nitro-L-arginine methylester [L NAME]) was added to the perfusate (50 mumol/liter and 1 mmol/liter as the final concentration, respectively). Lungs receiving saline served as controls. Gas exchange, hemodynamic and respiratory functions and the levels of cyclic 3',5'-guanosine monophosphate (cGMP) in the perfusate were measured. Results: Inhibition of NOS by L-NAME resulted in a significant (p < 0.01) increase in PVR (DeltaPV-R: 0.110 +/- 0.012 cm H2O/ml (.) min) within 5 minutes. In contrast, PVR was minimally affected by SnPP-9 (DeltaPVR: 0.005 +/- 0.005 cm H2O/ml (.) min), which was comparable to control lungs (DeltaPVR: 0.012 +/-10.005 cm H2O/ml (.) min). The level of cGMP in the perfusate 5 minutes after drug application was markedly, but not significantly, lower in the L-NAME group (1.67 +/- 0.74 nmol/liter) when compared with controls (2.69 +/- 0.89 nmol/liter) and SnPP79-treated lungs (2.65 +/- 0.66 nmol/liter). Conclusions: NOS but not HO contributes to the control of basal vascular tone in the rat lung.