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MODULATION OF HYPOXIC PULMONARY VASOCONSTRICTION BY ERYTHROCYTIC NITRIC OXIDE
Citation:
McMahon, T. F., Huang, YuhChin T, A. J. Gow, AND J. S. Stamler. MODULATION OF HYPOXIC PULMONARY VASOCONSTRICTION BY ERYTHROCYTIC NITRIC OXIDE. Presented at American Heart Association Meeting, San Diego, California, November 10-14, 2001.
Description:
Abstract
American Heart Association 2001
Modulation of Hypoxic Pulmonary Vasoconstriction by Erythrocytic NO
McMahon TJ1, Gow AJ1, Huang YCT4, Stamler JS1,2,3
Departments of Medicine1 and Biochemistry2, and Howard Hughes Medical Institute3,
Duke University Medical Center, Durham, NC 27710, and
US EPA4, Research Triangle Park, NC
Human red blood cells (RBCs) export NO-related bioactivity in concert with the hypoxia-induced allosteric transition in native S-nitrosohemoglobin (SNO-Hb) from the R (relaxed, oxy) to the T (tense, deoxy) structure. This mechanism may contribute to the vasodilator response to hypoxia in systemic vascular beds. In the lung, by contrast, hypoxia causes vasoconstriction in a manner that is proportional to hematocrit. The role of erythrocytic NO in hypoxic pulmonary vasoconstriction (HPV) is not known. We compared HPV in the presence of native human RBCs (C-RBCs) or RBCs enriched with NO (SNO-RBCs) in the isolated, buffer-perfused rabbit lung. Levels of SNO-Hb were increased in NO-RBCs relative to controls. Neither RBC preparation changed baseline pulmonary artery pressure (PAP) substantially. HPV was blunted in the presence of NO-RBCs relative to C-RBCs. Similarly, HPV was greater in the presence of Hb than in the presence of SNO-Hb. In rabbit pulmonary artery rings made hypoxic (~1% O2), SNO-Hb elicited vasodilation, while Hb caused vasoconstriction. Taken together, these findings suggest that erythrocytic Hb-bound NO may modulate hypoxic vasoconstriction in the lung. The ability to manipulate the O2-dependent bioactivity of RBCs may be useful in the treatment of ischemic syndromes and in efforts to improve outcomes associated with the use of RBC transfusions.
Abstract
American Heart Association 2001
Modulation of Hypoxic Pulmonary Vasoconstriction by Erythrocytic NO
McMahon TJ1, Gow AJ1, Huang YCT4, Stamler JS1,2,3
Departments of Medicine1 and Biochemistry2, and Howard Hughes Medical Institute3,
Duke University Medical Center, Durham, NC 27710, and
US EPA4, Research Triangle Park, NC
Human red blood cells (RBCs) export NO-related bioactivity in concert with the hypoxia-induced allosteric transition in native S-nitrosohemoglobin (SNO-Hb) from the R (relaxed, oxy) to the T (tense, deoxy) structure. This mechanism may contribute to the vasodilator response to hypoxia in systemic vascular beds. In the lung, by contrast, hypoxia causes vasoconstriction in a manner that is proportional to hematocrit. The role of erythrocytic NO in hypoxic pulmonary vasoconstriction (HPV) is not known. We compared HPV in the presence of native human RBCs (C-RBCs) or RBCs enriched with NO (SNO-RBCs) in the isolated, buffer-perfused rabbit lung. Levels of SNO-Hb were increased in NO-RBCs relative to controls. Neither RBC preparation changed baseline pulmonary artery pressure (PAP) substantially. HPV was blunted in the presence of NO-RBCs relative to C-RBCs. Similarly, HPV was greater in the presence of Hb than in the presence of SNO-Hb. In rabbit pulmonary artery rings made hypoxic (~1% O2), SNO-Hb elicited vasodilation, while Hb caused vasoconstriction. Taken together, these findings suggest that erythrocytic Hb-bound NO may modulate hypoxic vasoconstriction in the lung. The ability to manipulate the O2-dependent bioactivity of RBCs may be useful in the treatment of ischemic syndromes and in efforts to improve outcomes associated with the use of RBC transfusions.
Human red blood cells (RBCs) export NO-related bioactivity in concert with the hypoxia-induced allosteric transition in native S-nitrosohemoglobin (SNO-Hb) from the R (relaxed, oxy) to the T (tense, deoxy) structure. This mechanism may contribute to the vasodilator response to hypoxia in systematic vascular beds. In the lung, by contrast, hypoxia causes vasocontruction in a manner that is proportional to hematocrit.