Modulating Vascular Hemodynamics With an Alpha Globin Mimetic Peptide (HbαX).
The ability of hemoglobin to scavenge the potent vasodilator nitric oxide (NO) in the blood has been well established as a mechanism of vascular tone homeostasis. In endothelial cells, the alpha chain of hemoglobin (hereafter, alpha globin) and endothelial NO synthase form a macromolecular complex, providing a sink for NO directly adjacent to the production source. We have developed an alpha globin mimetic peptide (named HbαX) that displaces endogenous alpha globin and increases bioavailable NO for vasodilation. Here we show that, in vivo, HbαX administration increases capillary oxygenation and blood flow in arterioles acutely and produces a sustained decrease in systolic blood pressure in normal and angiotensin II-induced hypertensive states. HbαX acts with high specificity and affinity to endothelial NO synthase, without toxicity to liver and kidney and no effect on p50 of O2binding in red blood cells. In human vasculature, HbαX blunts vasoconstrictive response to cumulative doses of phenylephrine, a potent constricting agent. By binding to endothelial NO synthase and displacing endogenous alpha globin, HbαX modulates important metrics of vascular function, increasing vasodilation and flow in the resistance vasculature.
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
T C Stevenson
TC
Keller
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Joshua T
JT
Butcher
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Gilson Brás
GB
Broseghini-Filho
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Corina
C
Marziano
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Leon J
LJ
DeLalio
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Stephen
S
Rogers
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Bo
B
Ning
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Jennifer N
JN
Martin
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Sylvia
S
Chechova
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Maya
M
Cabot
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Xiahong
X
Shu
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Angela K
AK
Best
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Miranda E
ME
Good
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Alessandra
A
Simão Padilha
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Michael
M
Purdy
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Mark
M
Yeager
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Shayn M
SM
Peirce
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Song
S
Hu
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Allan
A
Doctor
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Eugene
E
Barrett
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Thu H
TH
Le
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.).
Linda
L
Columbus
From the Department of Molecular Physiology and Biological Physics (T.C.S.K., C.M., M.C., M.P., M.Y., B.E.I.), Robert M. Berne Cardiovascular Research Center (T.C.S.K., J.T.B., G.B.B.-F., C.M., L.J.D., X.S., A.K.B., M.E.G., B.E.I.), Department of Pharmacology (L.J.D.), Division of Nephrology, Department of Medicine (S.C., T.H.L.), and Division of Endocrinology, Department of Medicine (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Physiological Sciences, Federal University of Espirito Santa, Brazil (G.B.B.-F., A.S.P.); Departments of Pediatrics and Biochemistry, Washington University in Saint Louis, MO (S.R., A.D.); Department of Biomedical Engineering (B.N., S.M.P., S.H.) and Department of Chemistry (J.N.M., L.C.), University of Virginia, Charlottesville; and College of Pharmacy, Dalian Medical University, Dalian, China (X.S.). brant@virginia.edu.
Brant E
BE
Isakson
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011897:Random Allocation; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D055542:alpha-Globins / Q000378:metabolism*
D014665:Vasodilator Agents; D055542:alpha-Globins; D000804:Angiotensin II; D019001:Nitric Oxide Synthase
alpha globin; blood pressure; endothelial nitric oxide synthase; endothelium; mimetic peptide