| Nitric oxide causes hyporeactivity to phenylephrine in isolated perfused livers from endotoxin-treated rats. | |
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MedLine Citation:
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PMID: 7840201 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Systemic vascular hyporeactivity to vasoconstrictors has been described in rats following endotoxin administration. Inducible nitric oxide synthase (iNOS) expression is known to occur in the liver in endotoxemia, but consequences of iNOS induction on hepatic hemodynamics are unknown. The reactivity of the hepatic circulation to phenylephrine was tested in perfused livers from normal rats and rats previously injected with endotoxin (20 mg/kg ip). In control rats (n = 5), phenylephrine-induced portal pressure increases were similar in livers perfused with Krebs-Henseleit-bicarbonate (KHB) buffer, KHB plus the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA, 1 mM), or KHB plus the substrate for NO synthesis, L-arginine (1 mM). In contrast, livers from endotoxin-treated rats (n = 5) exhibited a marked reduction in the vasoconstrictive response to phenylephrine (14.6 vs. 55.1% in livers from control rats, P < 0.05). Perfusion with L-NMMA restored the phenylephrine response, and the L-NMMA effect was reversible with L-arginine. Perfusate NO2-/NO3- and guanosine 3',5'-cyclic monophosphate (cGMP) levels were increased in endotoxin-treated rats and significantly reduced by L-NMMA perfusion. In control livers, the NO donor S-nitroso-N-acetyl-DL-penicillamine blocked the portal pressure increase after phenylephrine administration. These results suggest that rat hepatic circulation takes part in the systemic vascular hyporeactivity to vasoconstrictors observed in endotoxemia and that NO is involved in this hyporeactivity to phenylephrine. |
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Authors:
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C M Pastor; T R Billiar |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The American journal of physiology Volume: 268 ISSN: 0002-9513 ISO Abbreviation: Am. J. Physiol. Publication Date: 1995 Jan |
Date Detail:
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Created Date: 1995-02-28 Completed Date: 1995-02-28 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0370511 Medline TA: Am J Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: G177-82 Citation Subset: IM |
Affiliation:
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Department of Surgery, University of Pittsburgh, Pennsylvania 15261. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arginine / analogs & derivatives, pharmacology Blood Pressure / drug effects Endotoxins / pharmacology* Escherichia coli Glucose / pharmacology Liver / drug effects* Male Nitric Oxide / antagonists & inhibitors, physiology* Penicillamine / analogs & derivatives, pharmacology Perfusion Phenylephrine / pharmacology* Portal System / drug effects, physiology Rats Rats, Sprague-Dawley Regional Blood Flow / drug effects S-Nitroso-N-Acetylpenicillamine Tromethamine / pharmacology Vasoconstriction Vasodilator Agents / pharmacology omega-N-Methylarginine |
| Grant Support | |
ID/Acronym/Agency:
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GM-44100/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Endotoxins; 0/Krebs-Henseleit solution; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 17035-90-4/omega-N-Methylarginine; 50-99-7/Glucose; 52-67-5/Penicillamine; 59-42-7/Phenylephrine; 74-79-3/Arginine; 77-86-1/Tromethamine; 79032-48-7/S-Nitroso-N-Acetylpenicillamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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