The effects of chronic nitric oxide synthase suppression on glioma pathophysiology

Abstract Nitric oxide synthase (NOS) is strongly expressed in glioma and has an important role in tumour blood flow (TBF) regulation. Whether manipulation of NOS function within a tumour can have any therapeutic effect is unknown. This study therefore evaluated the pathophysiological effects of chro...

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Published in:	British journal of neurosurgery Vol. 14; no. 6; pp. 543 - 548
Main Authors:	SWAROOP, G. R, KELLY, P. A. T, BELL, H. S, SHINODA, J, S.YAMAGUCHI, WHITTLE, I. R
Format:	Journal Article
Language:	English
Published:	Abingdon Informa UK Ltd 01-12-2000 Taylor & Francis Taylor & Francis Ltd
Subjects:	Animals Biochemistry Biological and medical sciences Blood Brain Brain Neoplasms - blood supply Brain Neoplasms - pathology Brain Neoplasms - physiopathology Brain Tumour Glioma Nitric Oxide Nitric Oxide Synthase Cerebrovascular Circulation - drug effects Drug Administration Schedule Enzyme Inhibitors - pharmacology Glioma - blood supply Glioma - pathology Glioma - physiopathology Medical research Medical sciences Necrosis Neoplasm Transplantation Neurology NG-Nitroarginine Methyl Ester - pharmacology Nitric Oxide Synthase - antagonists & inhibitors Nitric Oxide Synthase - metabolism Rats Regional Blood Flow - drug effects Tumors Tumors of the nervous system. Phacomatoses Intracranial Animal model Nervous system diseases Pathophysiology Rat Enzyme Immunocytochemistry Rodentia Malignant tumor Nitric-oxide synthase Cerebral disorder Pathology Autoradiography Malignant glioma Vertebrata Mammalia Animal Central nervous system disease Oxidoreductases Inhibition
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Summary:	Abstract Nitric oxide synthase (NOS) is strongly expressed in glioma and has an important role in tumour blood flow (TBF) regulation. Whether manipulation of NOS function within a tumour can have any therapeutic effect is unknown. This study therefore evaluated the pathophysiological effects of chronic systemic NOS inhibition on experimental rodent glioma blood flow, growth and necrosis.To determine the duration and pathophysiological effects of systemic NOS inhibition, Ng-nitroL-arginine methyl ester (L-NAME) was given to rats bearing C6 glioma acutely (single dose i.v., 30 mg kg) or for either 4 or 7 days (i.p. 75 mg kg day) prior to study.TBF and local cerebral blood flow (LCBF) were measured using C14-iodoantipyrine quantitative autoradiography. Tumour volume, tumoural necrosis and tumoural NOS were measured using conventional neuropathology and immunocytochemistry.Acute and 4-day L-NAME administration produced significant TBF reductions (48 and 39%, respectively) with less marked changes in LCBF (35 and 15%, respectively). Seven-day L-NAME administration reduced tumour volume ( p =0.12), increased tumoural necrosis ( p <0.05), but immunohistochemistry showed no difference in tumoural NOS expression. These results confirm that NOS has a significant role in the pathophysiology of experimental glioma, and that in this glioma model the effects of chronic systemic NOS inhibition are, for the period under study, predominately anti-tumoural. Whether chronic NOS inhibition is useful as an adjunct in glioma therapy or provides the opportunity for novel therapeutic approaches requires further study.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0268-8697 1360-046X
DOI:	10.1080/02688690020005554