| Modulation of the NO/cGMP pathway reduces the vasoconstriction induced by acellular and PEGylated haemoglobin. | |
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MedLine Citation:
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PMID: 18241681 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation of the NO/cGMP pathway modulates smooth muscle cells relaxation and hence vasoconstriction, a major hindrance for the use of cell-free haemoglobin (Hb) as blood substitute, despite conjugation with 5-kDa maleimide poly(ethylene)-glycol (PEG) reduces vasoconstriction in vivo. We aimed at assessing how a recently developed PEGylated-Hb (Deoxy-PEGHb) and manipulation of the NO/cGMP pathway enable modulation of vasoconstriction in isolated rat hearts. Hearts were Langendorff-perfused with oxygenated Krebs-Henseleit (15 ml/min) while monitoring the coronary pressure (CPP) after injection (1 min) of 50 nM norepinephrine followed by a 1 microM Hb or Deoxy-PEGHb bolus, without altering the flow. Deoxy-PEGHb induced less vasoconstriction than Hb. Although the presence of PEG could contribute to vasoconstriction, Deoxy-PEGHb did not contain appreciable amounts of free PEG. Whereas reducing endothelial NO release by 0.2 mM L-NAME increased vasoconstriction, abolishing NO scavenging by Hb using its cyanomet derivative almost completely blunted it. Furthermore, maintaining intracellular cyclic GMP by inhibiting phosphodiesterase-5 with 0.02 mM sildenafil enabled control of Hb-induced vasoconstriction. We conclude that, although PEG-Hb represents a possible approach to limit Hb-induced vasoconstriction, manipulating the NO/cGMP pathway may provide a powerful way to circumvent this problem. |
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Authors:
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Anna Caretti; Monica Fantacci; Dario Caccia; Michele Perrella; Kenneth C Lowe; Michele Samaja |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2008-01-05 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1784 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-09-23 Completed Date: 2008-12-31 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1428-34 Citation Subset: IM |
Affiliation:
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Dipartimento di Medicina, Chirurgia e Odontoiatria, University of Milan, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / drug effects Coronary Vessels / drug effects, physiology Cyclic GMP / physiology* Endotoxins / toxicity Heart / drug effects, physiology, physiopathology* Hemoglobins / adverse effects, therapeutic use* Male Muscle Relaxation / physiology Muscle, Smooth / blood supply, physiology Nitric Oxide / physiology* Perfusion / methods Polyethylene Glycols / adverse effects* Rats Rats, Sprague-Dawley Vasoconstriction / drug effects, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Endotoxins; 0/Hemoglobins; 0/Polyethylene Glycols; 10102-43-9/Nitric Oxide; 7665-99-8/Cyclic GMP |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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