Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 82: 1826-1835, 1997;
8750-7587/97 $5.00
This Article
Right arrow Full Text Free
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rudolph, A. S.
Right arrow Articles by Feuerstein, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rudolph, A. S.
Right arrow Articles by Feuerstein, G.

Journal of Applied Physiology
Vol. 82, No. 6, pp. 1826-1835, June 1997
SYSTEMIC CIRCULATION AND FLUID BALANCE

Liposome encapsulation attenuates hemoglobin-induced vasoconstriction in rabbit arterial segments

Alan S. Rudolph1, Anthony Sulpizio2, Paul Hieble2, Victor Macdonald3, Mark Chavez3, and Giora Feuerstein2

1 Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, Washington 20375-5348; 2 Department of Cardiovascular Pharmacology, SmithKline Beecham, King of Prussia, Pennsylvania 19406; and 3 Blood Research Detachment, Walter Reed Army Institute of Research, Washington, District of Columbia 20307

Received 16 April 1996; accepted in final form 29 January 1997.

Rudolph, Alan S., Anthony Sulpizio, Paul Hieble, Victor Macdonald, Mark Chavez, and Giora Feuerstein. Liposome encapsulation attenuates hemoglobin-induced vasoconstriction in rabbit arterial segments. J. Appl. Physiol. 82(6): 1826-1835, 1997.---Free hemoglobin (Hb) induces a potent vasoconstrictor response that may limit its therapeutic application as a red blood cell replacement. We have investigated whether encapsulation of stroma-free Hb (SFHb) or cross-linked Hb (alpha alpha -Hb) in liposomes modulates Hb vasoactivity in isolated blood vessels. Relaxation of rabbit thoracic vessels was measured before and after exposure to acellular SFHb, alpha alpha -Hb, and liposome-encapsulated SFHb or alpha alpha -Hb. SFHb and alpha alpha -Hb caused significant inhibition of carbachol-induced relaxation at 0.5 mg/dl, whereas encapsulation inhibited vessel relaxation at 30- to 60-fold higher Hb concentrations. The contractile response of rabbit ear arterial segments to electrical stimulation in the presence of acellular alpha alpha -Hb resulted in a 150% increase (EC150) in contractile amplitude at 0.23 mg/dl, whereas the EC150 for encapsulated alpha alpha -Hb was 13.7 mg/dl. Mechanistic studies of the vasoconstrictor activity of Hb demonstrated that acellular alpha alpha -Hb had no effect on norepinephrine release in the rabbit ear artery. In addition, neither acellular nor encapsulated alpha alpha -Hb preparations inhibited endothelial nitric oxide (NO) synthase activity isolated from bovine pulmonary artery. However, inhibition of vessel relaxation by acellular or encapsulated alpha alpha -Hb was reversed by the NO donor S-nitrosylpenacillamine, implicating Hb-NO binding as a possible mechanism for the vasoconstrictor response. In vitro stopped-flow kinetic studies of Hb-NO binding showed similar rates of reaction for conversion of oxyhemoglobin to methemoglobin (metHb; <2 ms), followed by rapid conversion of metHb to NO-Hb (300 ms) for both acellular and encapsulated alpha alpha -Hb, demonstrating that liposome encapsulation does not retard NO-Hb binding. The attenuated vasoactivity of encapsulated Hb may, therefore, result from the limited access of encapsulated Hb to NO imposed by the physical size of the liposome and reduced penetration of Hb across the vascular endothelium.

nitric oxide; blood substitute




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
H. Sakai, A. Sato, K. Masuda, S. Takeoka, and E. Tsuchida
Encapsulation of Concentrated Hemoglobin Solution in Phospholipid Vesicles Retards the Reaction with NO, but Not CO, by Intracellular Diffusion Barrier
J. Biol. Chem., January 18, 2008; 283(3): 1508 - 1517.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
V. Awasthi, S.-H. Yee, P. Jerabek, B. Goins, and W. T. Phillips
Cerebral oxygen delivery by liposome-encapsulated hemoglobin: a positron-emission tomographic evaluation in a rat model of hemorrhagic shock
J Appl Physiol, July 1, 2007; 103(1): 28 - 38.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
H. Sakai, H. Hara, M. Yuasa, A. G. Tsai, S. Takeoka, E. Tsuchida, and M. Intaglietta
Molecular dimensions of Hb-based O2 carriers determine constriction of resistance arteries and hypertension
Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H908 - H915.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X. Liu, M. J. S. Miller, M. S. Joshi, H. Sadowska-Krowicka, D. A. Clark, and J. R. Lancaster Jr.
Diffusion-limited Reaction of Free Nitric Oxide with Erythrocytes
J. Biol. Chem., July 24, 1998; 273(30): 18709 - 18713.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online