Hemoglobin-induced contraction of pig pulmonary veins.
The effects of hemoglobin Ao (HbAo), alpha alpha cross-linked hemoglobin (alpha alphaHb), cyanomet alpha alpha cross-linked hemoglobin (cyanomet alpha alphaHb), 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% O2/5% CO2. Increasing concentrations of HbAo and alpha alphaHb (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, respectively. Cyanomet alpha alphaHb and HSA (10(-9) - 3 x 10(-6) mol/L) did not cause significant increases in tension. The maximum responses to HbAo and alpha alphaHb 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 HbAo and alpha alphaHb. 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.
Muldoon
S M
SM
Uniformed Services University of the Health Sciences, Department of Anesthesiology, Bethesda, MD 20814, USA.
Ledvina
M A
MA
Hart
J L
JL
Macdonald
V W
VW
D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D012709:Serum Albumin / Q000494:pharmacology; D013552:Swine; D014680:Veins / Q000187:drug effects* / Q000502:physiology
D006454:Hemoglobins; D012709:Serum Albumin; D009569:Nitric Oxide; D012701:Serotonin; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin