Effect of age on angiotensin II-mediated downregulation of adrenomedullary catecholamine biosynthetic enzymes.
Expression of catecholamine biosynthesizing enzymes, tyrosine hydroxylase (TH) and dopamine beta hydroxylase (DbetaH) increase with age in the adrenal medulla, however, the underlying mechanisms are unclear. In the present study, we examined the effect of peripheral angiotensin II (AngII) on the expression of TH and DbetaH, in the adrenal medulla of young (6 mo) and old (23 mo) Fischer-344 rats. Saline or AngII (230 ng/kg/min sc) was infused for 3 days using osmotic minipumps. Adrenomedullary TH and DbetaH mRNA levels increased significantly with age, and while AngII reduced the expression of these enzymes in young animals, it had no such effect in the old animals. Neuropeptide Y (NPY), which is co-released with catecholamines in the adrenal medulla and stimulates the synthesis of TH and DbetaH, was also upregulated with age and downregulated in response to AngII in young rats. However, in the old animals, the already elevated NPY expression remained unchanged following AngII treatment. This data indicate that the hypertensive effect of peripheral AngII is compensated by an inhibition of adrenomedullary catecholamine biosynthesis in young animals, but this mechanism is impaired in senescence, potentially contributing to the age-related increase in catecholamine biosynthesis.
Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, FL 32608, USA. erdos@ufl.edu
Benedek
B
Erdös
S Remzi
SR
Erdem
Aysen
A
Erdem
Christopher S
CS
Broxson
Nihal
N
Tümer
D000313:Adrenal Medulla / Q000187:drug effects / Q000201:enzymology*; D000375:Aging / Q000502:physiology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004299:Dopamine beta-Hydroxylase / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D009478:Neuropeptide Y / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics
D009478:Neuropeptide Y; D012333:RNA, Messenger; D000804:Angiotensin II; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase