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135 EFFECTS OF AGING AND THE ANTIHYPERTENSIVE DRUG RILMENIDINE ON NERVE GROWTH FACTOR EXPRESSION IN THE SPLEEN OF MALE F344 RATS.
  1. J. Gross1,
  2. S. Vyas1,
  3. C. A. Molinaro1,
  4. S. Perez1,
  5. B. Millar1,
  6. J. Carter1,
  7. S. Flowers1,
  8. S. ThyagaRajan1,
  9. D. L. Bellinger1
  1. 1Department of Pathology and Anatomy, School of Medicine, Loma Linda University, Loma Linda, CA.

Abstract

Previous research in our laboratory showed an age-related decline in noradrenergic (NA) sympathetic innervation of spleens from male Fischer 344 (F344) rats. Since nerve growth factor (NGF) plays an important role in determining the density of sympathetic innervation of target tissues throughout life, dysregulation of NGF expression in splenic target cells might explain the loss of sympathetic nerves. Moreover, chronically heightened sympathetic activity can also destroy nerve terminals by increased oxidative stress resulting from the breakdown of norepinephrine. The purpose of this study was to investigate whether these mechanisms are responsible for the age-related loss of splenic sympathetic nerves. Western blot analysis of NGF protein expression was evaluated in splenic lysates from untreated young (3 month) and old (18 month) male F344 rats and from 15-month-old rats treated with vehicle or rilmenidine (0.5 mg/kg and 1.5 mg/kg, bid [IP]) for 3 months to down-regulation of sympathetic activity. Our studies showed a 40% decrease in NGF protein levels in spleens from old rats compared with young adults. Noteworthy, rilmenidine induced a dose-dependent effect on NGF protein levels: administration of low and high doses of rilmenidine increased splenic NGF levels by 60 and 50%, respectively, compared with the vehicle group (sterile physiologic saline). Splenic NGF levels in the low-dose rilmenidine-treated group (500 μg/kg) were not different from those in 3-month-old F344 rats. Collectively, these findings support our hypothesis that changes in NGF protein expression might explain, at least in part, the age-related decline in sympathetic innervation of the spleen. Furthermore our data suggest that age-related changes in sympathetic activity in the spleen during middle age may precipitate the loss of NGF protein in spleens from old F344 male rats.

This research is supported by NIH grant NS44032.

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