Abstract 085: Anti-Inflammatory Treatment Reverses The Age-Related Increase In Catecholamine Biosynthetic Enzyme Tyrosine Hydroxylase And NYP In The Adrenal Medulla

Abstract

Aging is associated with both elevated blood pressure and decreased baroreceptor sensitivity. These have been attributed to increased sympathetic nerve activity with age. One marker of sympathoactivation is protein levels of tyrosine hydoxylase (TH) in the adrenal medulla (AM), and TH levels markedly increase with age. There is also an increase in inflammation with age. To test the hypothesis that increased inflammation with age contributes to the elevated TH levels in the AM, we examined treatment with the anti-inflammatory agents, indomethacin (10 mg/kg, BID) or rosiglitazone (1 mg/kg, BID) on TH synthesis in F344 rats of three ages, 5, 12, 18 months. In addition, NPY, a peptide that is synthesized and co-released with catecholamines in the AM, as well as angiotensin II receptor subtypes, AT1 and AT2 protein levels were assessed in the AM following the anti-inflammatory treatments. Indomethacin and rosiglitazone were administered orally as part of a frozen strawberry treat for 16 days. Although there were no changes in TH or NPY levels between the 5 mo and 12 mo old control animals, TH and NPY were elevated by 27% and 45% (P<0.05), respectively in the 18 compared with 5 mo rats. These age-related increases were completely reversed by treatment with indomethacin or rosiglitazone (P<0.05). There was no effect of either treatment on AT1 or AT2 receptor protein, although AT1 receptor protein levels diminished slightly with age. These data indicate that anti-inflammatory treatment reverses the elevated TH and NPY in AM with age. Increased inflammation with age indirectly through elevated catecholamine synthesis may be contributing to the increased prevalence of hypertension with age.