NITRIC OXIDE-RELATED VASOCONSTRICTION IN LUNGS PERFUSED WITH RED-CELLLYSATE

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 Earl e's balanced salt solution (EBSS)] triggered profound and sustained va soconstriction, Vasoconstriction was not observed when . NO was added to lungs perfused with washed intact rat or human RBC or with oxyhemog lobin (Hgb 20 mu M). The presence of hemolysate in the perfusate also caused vasoconstriction in response to n-acetylcysteine (50 mu M), glu tathione (10(-4) M), or ascorbic acid (10(-4) M) and potentiated great ly the vasoconstrictor response to 5 mM KCl. Not only . NO, but also n itroprusside (SNP) or L-arginine and paradoxically three . NO synthesi s inhibitors, including N-monomethyl L-arginine, L-NAME, and nitroblue tetrazolium, which have different mechanisms of action, each caused i n the presence of hemolysate large vasoconstrictive responses. Hemolys ate itself enhanced O-2 consumption by slices of lung; no effects of t his 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 s uperoxide dismutase (SOD) and catalase (CAT) to the hemolysate contain ing perfusate, or addition of a cyclooxygenase or 5-lipoxygenase inhib itor, virtually abolished the . NO induced vasoconstriction. The latte r data are consistent with the concept that exposure of the vasculatur e 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 mitochondria l function, yet the precise molecular mechanisms responsible for the a ction of hemolysate are likely to be very complex.