Effect of age on angiotensin II-mediated downregulation of adrenomedullary catecholamine biosynthetic enzymes

Erdös, Benedek; Erdem, Remzi; Erdem, Ayşen; Broxson, Christopher; Tümer, Nihal

doi:10.1016/j.exger.2008.04.012

Cited by 3 publications

(4 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TH catalyzes the hydroxylation of tyrosine, producing dopamine, whereas DβH catalyzes the conversion of catecholamines from the adrenal medulla. We and others have shown that the levels of catecholamine biosynthetic enzymes 15 - 18 , 55 and NPY increase with age in the adrenal medulla 19 , 20 , 22 , 56 . In present study, resveratrol treatment normalized the levels of DβH and NPY in the adrenal medulla of aged rats.…”

Section: Discussionmentioning

confidence: 74%

Age Impaired Endothelium-Dependent Vasodilation is Improved by Resveratrol in Rat Mesenteric Arteries

Göçmez

Scarpace

Whidden

et al. 2016

Journal of Exercise Nutrition &Amp; Biochemistry

View full text Add to dashboard Cite

[Purpose]To determine whether resveratrol improves the adverse effects age on vascular function in mesenteric arteries (MAs), and diminishes the hyperactivity in adrenal gland with age.[Methods]Male F344 x Brown Norway rats were assigned to 6-month control (YC), 6-month resveratrol (YR), 24-month control (OC) and 24-month resveratrol (OR). Resveratrol (15 mg/kg) was provided to resveratrol groups in drinking water for 14 days.[Results]Concentration response curves to phenylephrine (PE, 10-9-10-5M), acetylcholine (Ach, 10-9-10-5M) and resveratrol (10-8-10-4M) were evaluated in pressurized isolated MAs. The Ach concentration-response curve was right shifted with maximal response diminished in OC compared with YC rats. These effects were reversed by resveratrol treatment. The resveratrol-mediated relaxant responses were unchanged with age or resveratrol suggesting an endothelium-independent mechanism. Resveratrol tended to increase endothelial nitric oxide synthase; caused no effect on copper-zinc superoxide dismutase; and normalized the age-related elevatation in DβH and NPY levels in adrenal medulla, two indicators of sympathetic activity[Conclusion]These data indicate that resveratrol reverses age-related dysfunction in endothelium-dependent vasodilation in MAs and partially reverses hyperactivity of adrenomedullary function with age. This treatment may have a therapeuticpotential in the treatment of cardiovascular diseases or hypertension in the elderly.

show abstract

Section: Discussionmentioning

confidence: 74%

Age Impaired Endothelium-Dependent Vasodilation is Improved by Resveratrol in Rat Mesenteric Arteries

Göçmez

Scarpace

Whidden

et al. 2016

Journal of Exercise Nutrition &Amp; Biochemistry

View full text Add to dashboard Cite

show abstract

“…First, as our previous studies have indicated, BP of old rats is less sensitive to centrally infused ANG II, and restraint stress-induced BP elevation is also diminished with age (13) despite the fact that both ANG II-and stress-induced hypertensive responses are mediated by superoxide anion (11,26,27). However, one important target of the ANG II-superoxide pathway is noradrenergic neurons in the hypothalamus and brain stem (7,18,46), and we have shown in previous studies that hypothalamic levels of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, and dopamine ␤-hydroxylase are reduced markedly in old animals compared with young (9,14). Although it is not yet clear whether this is due to a loss of noradrenergic cells in cardiovascular regulatory regions or to reduced catecholamine biosynthesis, it is possible that a decline in noradrenergic neurotransmission limits the ability of superoxide anion to increase SNS activity and BP.…”

Section: Long-term Cardiovascular Effects Of Hf Feedingmentioning

confidence: 75%

Effect of age on high-fat diet-induced hypertension

Erdös

Kirichenko

Whidden

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Aging and obesity both have a significant impact on central blood pressure (BP) regulation, and previous studies indicated that changes in central redox signaling with age may affect high-fat (HF) diet-induced cardiovascular responses. Therefore, we investigated the effects of 60% HF feeding on BP regulation in young adult (5 mo) and old (26 mo) Fischer-344 × Brown-Norway rats. Radiotelemetric transmitters were implanted to measure BP, heart rate (HR), locomotor activity, and spontaneous baroreflex sensitivity. Expression and activity of NADPH oxidase and ANG II type 1 receptor were assessed in the hypothalamus and in the nucleus tractus solitarii. Old animals gained more weight on HF diet compared with young, whereas central NADPH oxidase expression and activity elevated similarly in the two age groups. After an initial hypotensive and tachycardic response during the first week of HF feeding, BP in young animals increased and became significantly elevated after 6 wk of HF feeding. In contrast, BP in old animals remained depressed. Nighttime HR and locomotor activity decreased in both young and old rats fed with HF diet, but these changes were more significant in young rats. As a result, amplitudes of circadian variation of BP, HR, and activity that were originally higher in young rats declined significantly and became similar in the two age groups. In conclusion, our experiments led to the surprising finding that HF diet has a more serious impact on cardiovascular regulation in young animals compared with old.

show abstract

“…7). Moreover, levels of enzymes involved in the metabolism of catecholamines have been shown to be increased with aging in the medulla [10,11,12], thus potentially worsening the situation. Interestingly, adjacent tissues can be affected as well, as exemplified by the zona reticularis of the AC in our study (fig.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, less is known about aging-induced structural changes in the AM, the catecholaminergic part of the gland. However, at the molecular level, it has been shown that levels of catecholaminergic enzymes are increased upon aging in the medulla of rodents [10,11,12]. …”

Section: Introductionmentioning

confidence: 99%

Catecholamine Metabolism Induces Mitochondrial DNA Deletions and Leads to Severe Adrenal Degeneration during Aging

et al. 2016

View full text Add to dashboard Cite

Background: Aging is a multifactorial process characterized by organ loss of function and degeneration, but the mechanisms involved remain elusive. We have shown recently that catecholamine metabolism drives the accumulation of mitochondrial DNA (mtDNA) deletions in dopaminergic cells, which likely contribute to their degeneration during aging. Here we investigated whether the well-documented degeneration and altered function of adrenals during aging is linked to catecholamine production in the medulla followed by accumulation of mtDNA deletions. Material and Methods: We analyzed adrenal medullary and cortical samples of both murine and human origin covering a wide range of ages for mtDNA deletion content, mtDNA copy number, mitochondrial and cellular integrity as well as aging-related tissue changes such as fibrosis. Results: Indeed, we demonstrate in mice and humans that the adrenal medulla accumulates a strikingly high amount of mtDNA deletions with age, causing mitochondrial dysfunction in the adrenal medulla, but also in the cortex, accompanied by apoptosis and, more importantly, by severe inflammation and remarkable fibrosis. Additionally, a concomitant and dramatic loss of medullary and cortical cells is observed in old animals. Conclusion: Our results show that accumulation of mtDNA deletions, and the ensuing mitochondrial dysfunction, is a hallmark of adrenal aging, further strengthening the hypothesis that catecholamine metabolism is detrimental to mtDNA integrity, mitochondrial function and cell survival. Moreover, the cell loss potentially induced by mitochondrial dysfunction could explain the decline in adrenal hormonal and steroidal secretion during aging.

show abstract

Effect of age on angiotensin II-mediated downregulation of adrenomedullary catecholamine biosynthetic enzymes

Cited by 3 publications

References 28 publications

Age Impaired Endothelium-Dependent Vasodilation is Improved by Resveratrol in Rat Mesenteric Arteries

Age Impaired Endothelium-Dependent Vasodilation is Improved by Resveratrol in Rat Mesenteric Arteries

Effect of age on high-fat diet-induced hypertension

Catecholamine Metabolism Induces Mitochondrial DNA Deletions and Leads to Severe Adrenal Degeneration during Aging

Contact Info

Product

Resources

About