Abstract
We previously reported that 27 day (d) rabbit fetuses born to does immunized against nerve growth factor (NGF) demonstrate extensive depletion of tissue catecholamines (CAT). Here we report results of studies with this model at 31 d gestation (term) and the effects of autoimmune sympathectomy on beta adrenergic receptor development. Virgin 12 wk old female rabbits were immunized with 100 μg 2.5S NGF and boosted monthly for 12 wks. Serum anti-NGF titers were determined by radioimmunoassay. Animals were then date bred and sacrificed at 31 d. Tissue CAT were determined by a sensitive, specific radioenzymatic assay. BAR were determined in pooled lungs from control or immunized litters by radioligand binding assay using dihydroalprenolol (DHA). Lung, heart, adrenal, paraaortic gland and brown adipose tissue CAT all were extensively decreased in animals with high anti-NGF titers (p<.001). Lower titers, which cause denervation at 27 d were not effective at 31 d. Lung BAR increased from 108 to 140 fmole bound DHA/mg protein following successful denervation (p<.05). Organ weight, carcass weight, survival and duration of gestation were unaffected by the immunization. Conclusions: 1) Organ sympathetic innervation in the fetal rabbit is dependent on NGF; 2) the extent of denervation in the autoimmune sympathectomy model is dependent upon NGF antibody titer; 3) fetal rabbit lung BAR are increased following denervation. Speculation: With advancing developmental age, the role of NGF in sympathetic innervation becomes less critical.
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