Hemoglobin-induced contraction of pig pulmonary veins

Abstract

The effects of hemoglobin A o (HbA o), αα cross-linked hemoglobin (ααHb), cyanomet αα cross-linked hemoglobin (cyanometααHb), and human serum albumin (HSA) were compared under basal conditions and during relaxation with acetylcholine (ACh), sodium nitroprusside (SNP), and papaverine (PAP) in porcine pulmonary 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% CO 2. Increasing concentrations of HbA o and ααHb (10 −9−3 × 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, respectively. CyanometααHb and HSA (10 −9− 3 × 10 −6mol/L) did not cause significant increases in tension. The maximum responses to HbA o and ααHb were significantly increased during relaxation 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 ααHb. These studies support the concept that hemoglobin-induced vascular contraction is primarily mediated by inactivation of the vasodilator nitric oxide in vitro. We suggest that this mechanism is common to acellular hemoglobins in which the ligand binding site is unimpaired and in which the heme iron is in the ferrous ( +2) state.