Document Detail

NG-methyl-L-arginine, an inhibitor of nitric oxide formation, reverses IL-2-mediated hypotension in dogs.
MedLine Citation:
PMID:  8005855     Owner:  NLM     Status:  MEDLINE    
The effects of NG-methyl-L-arginine (L-NMA), an inhibitor of nitric oxide formation, were studied in dogs treated with interleukin-2 (IL-2). The administration of IL-2 to dogs resulted in hypotension within 3 days of treatment. The development of hypotension correlated with accumulation in the serum of nitrate, which is a stable breakdown product of nitric oxide. Administration of L-NMA decreased serum nitrate levels and increased the mean arterial pressure. The antihypotensive effect was dose dependent with a maximum effect observed at a dose of 20 mg/kg. Administration of a continuous infusion of L-NMA (5 maintained the mean arterial pressure for 48 h with concurrent administration of IL-2. Evaluation of IL-2-induced lymphokine-activated killer cell proliferation and tumoricidal activity toward a canine glioblastoma target cell line was unaffected by L-NMA. These studies imply that L-NMA may effectively ameliorate the dose-limiting hypotension associated with administration of IL-2 without adversely affecting the antitumor effects.
R G Kilbourn; L B Owen-Schaub; D M Cromeens; S S Gross; M J Flaherty; S M Santee; A M Alak; O W Griffith
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  76     ISSN:  8750-7587     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  1994 Mar 
Date Detail:
Created Date:  1994-07-15     Completed Date:  1994-07-15     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1130-7     Citation Subset:  IM    
Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
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MeSH Terms
Antineoplastic Agents / pharmacology
Arginine / analogs & derivatives*,  pharmacology
Blood Pressure / drug effects
Blood Urea Nitrogen
Cell Division / drug effects
Creatinine / blood
Enzymes / blood
Glioma / metabolism,  physiopathology
Hypotension / chemically induced,  prevention & control*
Interleukin-2 / antagonists & inhibitors*,  pharmacology
Killer Cells, Lymphokine-Activated / drug effects
Leukocyte Count / drug effects
Lymphocytes / drug effects
Monocytes / drug effects
Nitric Oxide / antagonists & inhibitors*,  biosynthesis,  blood
Thrombocytopenia / chemically induced
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Antineoplastic Agents; 0/Enzymes; 0/Interleukin-2; 10102-43-9/Nitric Oxide; 17035-90-4/omega-N-Methylarginine; 60-27-5/Creatinine; 74-79-3/Arginine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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