HEMOGLOBIN-INDUCED CONTRACTION OF PIG PULMONARY VEINS

The effects of hemoglobin A(o) (HbA(o)), alpha alpha cross-linked hemo globin (alpha alpha Hb), cyanomet alpha alpha cross-linked hemoglobin (cyanomet alpha alpha Hb), and human serum albumin (HSA) were compared under basal conditions and during relaxation with acetylcholine (ACh) , sodium nitroprusside (SNP), and papaverine (PAP) in porcine pulmonar y veins. Isometric tension changes were recorded in isolated rings (3 to 4 mm) that were suspended in Krebs solution bubbled with 95% O-2/5% CO2. Increasing concentrations of HbA(o) and alpha alpha Hb (10(-9) - 3 x 10(-6) mol/L) caused concentration-dependent increases in tension that reached a maximum of 4.20 +/- 0.3 gm and 3.78 +/- 0.6 gm, respec tively. Cyanometor alpha alpha Hb and HSA (10(-9) - 3 x 10(-6) mol/L) did not cause significant increases in tension. The maximum responses to HbA(o) and alpha alpha Hb were significantly increased during relax ation with ACh and SNP but not with PAP, in contrast, SNP (10(-4) mol/ L) and PAP (10(-5) mol/L), but not ACh, reversed contractions induced by HbA(o) and alpha alpha Hb. These studies support the concept that h emoglobin-induced vascular contraction is primarily mediated by inacti vation of the vasodilator nitric oxide in vitro. We suggest that this mechanism is common to acellular hemoglobins in which the ligand bindi ng site is unimpaired and in which the heme iron is in the ferrous (()2) state.