Published online before print July 24, 2008, doi: 10.1161/CIRCRESAHA.108.176867
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on April 2, 2008
Revised on July 8, 2008
Accepted on July 16, 2008
Hypoxic Vasodilation by Red Blood Cells. Evidence for an S-Nitrosothiol–Based Signal
Diana L. Diesen ;
From the Departments of Surgery (D.L.D.), Medicine (D.T.H., J.S.S.), and Biochemistry (J.S.S.), Duke University Medical Center, Durham, NC 27710.
* To whom correspondence should be addressed. E-mail: staml001{at}mc.duke.edu.
Red blood cells (RBCs) have been ascribed an essential role in matching blood flow to local metabolic demand during hypoxic vasodilation. The vasodilatory function of RBCs evidently relies on the allosteric properties of hemoglobin (Hb), which couple the conformation of Hb to tissue oxygen tension (PO2) and thereby provide a basis for the graded vasodilatory activity that is inversely proportional to Hb oxygen saturation. Although a large body of evidence indicates that the PO2-coupled allosteric transition from R (oxy)-state to T (deoxy)-state subserves the release from Hb of vasodilatory nitric oxide (NO) bioactivity, it has not yet been determined whether the NO-based signal is a necessary and sufficient source of RBC-mediated vasoactivity and it has been suggested that ATP or nitrite may also contribute. We demonstrate here by bioassay that untreated human RBCs rapidly and substantially relax thoracic aorta from both rabbit and mouse at low PO2 (
1% O2) but not at high PO2 (21% O2). RBC-mediated vasorelaxation is inhibited by prior depletion of S-nitroso-Hb, potentiated by low-molecular-weight thiols, and dependent on cGMP. Furthermore, these relaxations are largely endothelium-independent and unaffected by NO synthase inhibition or nitrite. Robust relaxations by RBCs are also elicited in the absence of endothelial, neuronal or inducible NO synthase. Finally, contractions that appear following resolution of RBC-mediated relaxations are dependent on NO derived from RBCs as well as the endothelium. Our results suggest that an S-nitrosothiol–based signal originating from RBCs mediates hypoxic vasodilation by RBCs, and that vasorelaxation by RBCs dominates NO-based vasoconstriction under hypoxic conditions.
Key words: red blood cell • hemoglobin • nitric oxide • hypoxic vasodilation
Related Article:
- Transnitrosation Signals Oxyhemoglobin Desaturation
- Nadzeya Marozkina, Benjamin Gaston, and Allan Doctor
Circ. Res. 2008 103: 441-443.[Extract] [Full Text] [PDF]
This article has been cited by other articles:
 |
|
 |
|
  H. G. Bohlen, X. Zhou, J. L. Unthank, S. J. Miller, and R. Bills Transfer of nitric oxide by blood from upstream to downstream resistance vessels causes microvascular dilation Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1337 - H1346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Grande, C. Rippe, A. Rippe, A. Rahman, K. Sward, and B. Rippe Unaltered size selectivity of the glomerular filtration barrier in caveolin-1 knockout mice Am J Physiol Renal Physiol, August 1, 2009; 297(2): F257 - F262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Huang, S. C. Chen, and D. L. Wang Shear flow increases S-nitrosylation of proteins in endothelial cells Cardiovasc Res, August 1, 2009; 83(3): 536 - 546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Marozkina, B. Gaston, and A. Doctor Transnitrosation Signals Oxyhemoglobin Desaturation Circ. Res., August 29, 2008; 103(5): 441 - 443. [Full Text] [PDF]
|
|