Splenic sympathetic response to endotoxin is blunted in the fetal alcohol-exposed rat: role of nitric oxide.
This study was designed to test the hypothesis that nitric oxide (NO) mediates the blunted splenic sympathetic response to lipopolysaccharide (endotoxin) that occurs in young rats exposed to alcohol in utero (FAE). The subjects, 26-29-day-old rats, were progeny of pregnant dams fed an alcohol diet (35% of the calories were derived from ethanol) or their control and pair-fed (PFC) cohorts. We examined the effects of lipopolysaccharide (LPS) (0.5 mg/kg, i.p.) on splenic norepinephrine (NE) turnover, an index of sympathetic neural activity, splenic inducible NO synthase (iNOS) protein immunoreactivity, and NO metabolites nitrite/nitrate concentrations in plasma. In response to LPS, splenic NE turnover was increased by more than twofold in the PFC groups, but the increase did not occur in their FAE cohorts. The blockade of NOS with L-NAME (30 mg/kg, i.p.) reversed this difference. In both the PFC and FAE rats, basal levels of splenic iNOS protein immunoreactivity were equally barely detected and plasma NO metabolite levels were relatively low (25 microM in both groups). In response to LPS, however, iNOS protein displayed a marked increase in the PFC group and an even greater increase (by close to threefold) in the FAE rats. LPS also substantially increased plasma NO metabolite levels by close to eightfold in the control groups, but by 15-fold in their FAE cohorts compared to the basal levels. These findings support the hypothesis that in the FAE rat, an augmented NO formation accounts for the blunted sympathetic response to endotoxin.
Gottesfeld
Z
Z
Department of Neurobiology and Anatomy, University of Texas Medical School, Houston 77225, USA. zehavag@nba19.med.uth.tmc.edu
Maier
M
M
Mailman
D
D
Lai
M
M
Weisbrodt
N W
NW
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009638:Norepinephrine / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects*
D004731:Endotoxins; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D000431:Ethanol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine