Role of NO and endothelin in hemoglobin-induced pulmonary vasoconstriction

The underlying mechanisms of hemoglobin (Hb)-induced vasoconstriction are n ot yet well understood. The aim of this study was to elucidate the influenc e of nitric oxide (NO) and endothelin (ET) on Hb-induced pulmonary vasocons triction. Therefore, an autologous Hb preparation was administered into iso lated rabbit lungs, in which pulmonary artery pressure (PAP) and weight gai n was monitored. Either glyceroltrinitrate (GTN; 10(-5) M; n = 6), L-argini ne (10(-2) M; n = 6), L-NAME (10(-4)M; n = 6), ETA- or ETB-receptor antagon ists (BQ(123), 10(-6)M, n = 6) or (BQ(788), 10(-6) M, n = 6) were added to the perfusion fluid and NOx and thromboxane A, levels were measured. Result s: in the control group the Hb-stimulation resulted in a pressure response up to 25.1 +/- 2.1 mmHg (p < .05), which was 136 +/- 6% of the reference va lue. The PAP increase was significantly (p < .05) blunted after GTN (71 +/- 5%), L-arginine (93 +/- 6%) and BQ(788) (88 +/- 7%). Pretreatment with L-N AME (139 +/- 13%) or BQ(123) (115 +/- 9%) did not show significant changes in PAP. Conclusion: The reduction of the Hb-induced pulmonary hypertension by NO-donors points toward the inactivation of NO by free hemoglobin. Likew ise, ETB-receptor mediated vasoconstrictive effects without changes in NOx concentrations seem to play a pathogenetic role in the Hb-induced pulmonary vasoconstriction.