PERFUSATE VISCOSITY AND HEMATOCRIT DETERMINE PULMONARY VASCULAR RESPONSIVENESS TO NO SYNTHASE INHIBITORS

The pulmonary vascular responses to changes in perfusate viscosity wer e studied in isolated rat lungs treated with the nitric oxide synthase (NOS) inhibitors, N-omega-nitro-L-arginine methyl ester (L-NAME) and No-monomethyl-L-arginine (L-NMMA). Lungs were isolated according to st andard protocols and perfused with varying concentrations of albumin i n physiological salt solution (PSS) and with low, intermediate, and no rmal hematocrits using washed erythrocytes. Pressure-flow curves were generated by increasing pulmonary arterial pressure (P-PA) while keepi ng pulmonary venous pressure (P-PV) constant and measuring flow at eac h pressure interval. Neither perfusate flow nor pulmonary vascular res istance changed after L-NAME or L-NMMA (300 mu M) at any pressure inte rval in lungs perfused with 4 and 10% albumin/PSS. In lungs perfused w ith 20% albumin/PSS, L-NMMA decreased flow at all P-PA tested except 1 0 cmH(2)O (P < 0.05). L-NAME decreased flow in lungs perfused with nor mal (39.2 +/- 2.1%) hematocrits at all P-PA tested. Conversely, L-NAME decreased flow in lungs perfused with low and intermediate hematocrit s only at the highest pressure intervals. L-Arginine, when given after NOS inhibitors, failed to restore flow to baseline values in any grou p of lungs. N-omega-nitro-D-arginine methyl ester (300 mu M) did not c hange flow at any pressure interval in lungs perfused with normal (43 +/- 1.5%) hematocrit, washed erythrocytes. We conclude that lungs perf used with intermediate and normal hematocrit, washed erythrocytes, as well as with high-viscosity albumin/PSS solutions, show increased pulm onary vascular responses to NOS inhibitors.