NITRIC OXIDE-RELATED VASOCONSTRICTION IN LUNGS PERFUSED WITH RED-CELL LYSATE

The present study in isolated rat lungs demonstrates that nitric oxide gas (. NO, 70 nM) added to the perfusate containing a small amount of hemolysate [175 mu l of lysed red blood cells (RBC) per 50 ml of Earle's balanced salt solution (EBSS)] triggered profound and sustained vasoconstriction, Vasoconstriction was not observed when . NO was added to lungs perfused with washed intact rat or human RBC or with oxyhemoglobin (Hgb 20 mu M). The presence of hemolysate in the perfusate also caused vasoconstriction in response to n-acetylcysteine (50 mu M), glutathione (10(-4) M), or ascorbic acid (10(-4) M) and potentiated greatly the vasoconstrictor response to 5 mM KCl. Not only . NO, but also nitroprusside (SNP) or L-arginine and paradoxically three . NO synthesis inhibitors, including N-monomethyl L-arginine, L-NAME, and nitroblue tetrazolium, which have different mechanisms of action, each caused in the presence of hemolysate large vasoconstrictive responses. Hemolysate itself enhanced O-2 consumption by slices of lung; no effects of this dose of . NO on lung slice respiration were seen in the absence of hemolysate. Both Hgb and hemolysate lowered perfusate cGMP levels to the same degree suggesting that the vasoconstrictive response was not due to unique effects of hemolysate on guanylyl cyclase, Addition of superoxide dismutase (SOD) and catalase (CAT) to the hemolysate containing perfusate, or addition of a cyclooxygenase or 5-lipoxygenase inhibitor, virtually abolished the . NO induced vasoconstriction. The latter data are consistent with the concept that exposure of the vasculature to hemolysate may result in the formation of peroxynitrite. However, SOD and CAT did not abolish the pulmonary vasoconstriction induced by L-arginine or by NAG. Our data indicate that hemolysate has profound effects on lung vessel tone regulation and on lung tissue mitochondrial function, yet the precise molecular mechanisms responsible for the action of hemolysate are likely to be very complex.