Alcohol & Alcoholism Vol. 39, No. 2, pp. 101-105, 2004
Alcohol & Alcoholism Vol. 39, No. 2 © Medical Council on Alcohol 2004; all rights reserved.
BRAIN NITRIC OXIDE SYNTHASE LEVELS INCREASE IN RESPONSE TO ANTENATAL ETHANOL EXPOSURE
Departments of 1 Pediatrics and 2 Molecular Pharmacology, Northwestern University, Chicago, IL, 2Department of Pediatrics, Division of NeonatalPerinatal Medicine, Emory University, Atlanta, GA, 3 Department of Biomedical and Pharmaceutical Sciences and the 4 International Heart Institute of Montana, University of Montana, Missoula, MT, USA
* Author to whom correspondence should be addressed at: International Heart Institute of Montana, St Patrick Hospital, 500 W Broadway, Missoula, MT 59802, USA. Tel.: +406 327 1673; Fax: +406 329 5880; E-mail: smblack{at}selway.umt.edu
(Received 24 March 2003; first review notified 25 July 2003; in revised form 10 September 2003; accepted 25 November 2003)
Aims: Our previous in vitro data have indicated that ethanol can increase nitric oxide synthase (NOS) expression. Thus, the Aims of this study were to determine whether ethanol produces the same effect in vivo. Methods: To accomplish this, we utilized the well-established prenatal ethanol (EtOH) exposure model in the guinea pig to examine the effect on brain NOS expression and activity. Results: Brain homogenates isolated from offspring of guinea pigs fed EtOH exhibited an increase in NOS protein expression and NOS activity compared to controls. Increased expression of neuronal NOS was observed only in soluble fractions of brain homogenates (P < 0.05 vs. control). Increased expression of a
60 kDa band was detected in the soluble fraction that was immunoreactive against an antiserum raised against inducible NOS. In addition, an immunoreactive band of the correct predicted molecular weight for iNOS was found in the particulate fraction although the expression was unchanged between control and EtOH-treated animals. Endothelial NOS protein expression could not be detected in either soluble or particulate fractions from control or EtOH-treated animals. Conclusions: These results suggest that EtOH may exert its toxic effects antenatally via a mechanism of altered nitric oxide availability from NOS.
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