Hypertensive effects of central angiotensin II infusion and restraint stress are reduced with age

Erdös, Benedek; Cudykier, Idan; Woods, Mary; Başgut, Bilgen; Whidden, Melissa A.; Tawil, Rabih; Cardounel, Arturo J.; Tümer, Nihal

doi:10.1097/hjh.0b013e328338a075

Cited by 11 publications

(16 citation statements)

References 41 publications

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“…Consistent with previous studies [21,22,23], the present report demonstrates that BP increases significantly in old rats compared with that in the young, the pressor and tachycardic responses to stress and central AngII decreases with age, and adrenomedullar TH and DβH, and AT1 receptor mRNA expression increase with age, whereas hypothalamic TH decreases with age. Furthermore, hypothalamic Cu-ZnSOD and catalase levels decreased with age, and the increase in NADPH oxidase activity was associated with a corresponding increase in gp91 protein and p22 mRNA levels.…”

Section: Discussionsupporting

confidence: 92%

“…In our previous studies, we demonstrated that the age-dependent increase in BP is accompanied by increases in adrenomedullary TH, DβH, and neuropeptide Y levels, which are all indicators of the sympathetic nervous system activity [21,22,23]. In addition, restraint stress and central AngII-induced BP and HR elevations were reduced with age.…”

Section: Discussionmentioning

confidence: 97%

“…infusion of AngII significantly increased apocynin-sensitive production of superoxide in the hypothalamus, and provides further evidence that the production of superoxide by NADPH oxidase mediates the central effects of AngII. In addition, we found that hypothalamic antioxidant levels decreased, including nitrotyrosine and 4-hydroxynonenal, whereas p47 and p22 mRNA levels of NADPH oxidase subunits increased in old rats [21], [23]. These findings suggest that the increase in oxidative stress induced by the sympathetic nervous system activity and central AngII is a key pathogenic pathway for the development of age-related hypertension.…”

Section: Discussionmentioning

confidence: 98%

“…In addition, restraint stress and central AngII-induced BP and HR elevations were reduced with age. These age-related changes in cardiovascular responses and enzyme levels were diminished by central losartan, an AT1 receptor antagonist, and this effect was more pronounced in the young [21]. It is known that AngII-mediated cardiovascular responses are mediated by the NADPH oxidase-dependent superoxide signal [24,25,26].…”

Section: Discussionmentioning

confidence: 99%

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Effect of High-Salt Diet on Age-Related High Blood Pressure and Hypothalamic Redox Signaling

Başgut

Whidden²,

Kirichenko³

et al. 2017

Pharmacology

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Aim: The aim of this study was to investigate the effect of a high salt (HS) diet on age-related changes in blood pressure (BP) and the possible role played by regulatory central mechanisms. Methods: Young (5 months) and old (27 months) male Fischer 344 × Brown Norway (F344/BN) rats were fed standard chow or 8% HS diet for 12 days. BP and heart rate (HR) were measured by telemetry. Results: Mean arterial BP (MAP) was significantly elevated in old rats during the day and night when compared with young animals. The HS diet further elevated MAP in both age groups, and the increase was more pronounced in the old animals, while HR was not altered by age or HS diet. In addition, cardiovascular responses to restraint stress were diminished in the old when compared with the young and were unchanged with HS diet in either age group. Both age and the HS diet elevated the adrenomedullary mRNA levels of tyrosine hydroxylase, an indicator for sympathoexcitation. HS diet enhanced intracerebroventricular angiotensin II (AngII)-induced BP and HR elevations in both age groups. AngII type 1 receptor mRNA increased significantly in the hypothalamus with age and HS diet. Furthermore, hypothalamic p22^phox mRNA and gp91^phox protein, subunits of NADPH oxidase, as well as NADPH oxidase activity increased with the HS diet in the old animals, whereas antioxidant enzymes that decreased with age yet remained unaltered with the HS diet. Conclusion: Our findings indicate that sensitivity of BP to HS diet increases with age, and that central AngII-induced pressor responses are diminished in old rats compared with the young both under control conditions and during HS diet treatment. These changes are paralleled by increases in the expression and NADPH oxidase activity in the hypothalamus, possibly leading to central oxidative stress-mediated sympathoexcitation and high BP.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Effect of High-Salt Diet on Age-Related High Blood Pressure and Hypothalamic Redox Signaling

Başgut

Whidden²,

Kirichenko³

et al. 2017

Pharmacology

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“…An elevation in activity may also serve as a contributing mechanism for the negative energy balance. In this regard, a recent report considering the effect of aging on the hypertensive effects of Ang II noted that a similar dose of Ang II administered icv leads to elevated locomotor activity in both young and old rats (24).…”

Section: Discussionmentioning

confidence: 99%

Central angiotensin II has catabolic action at white and brown adipose tissue

Kloet

Krause

Scott

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Considerable evidence implicates the renin-angiotensin system (RAS) in the regulation of energy balance. To evaluate the role of the RAS in the central nervous system regulation of energy balance, we used osmotic minipumps to chronically administer angiotensin II (Ang II; icv; 0.7 ng/min for 24 days) to adult male Long-Evans rats, resulting in reduced food intake, body weight gain, and adiposity. The decrease in body weight and adiposity occurred relative to both ad libitum-and pair-fed controls, implying that reduced food intake in and of itself does not underlie all of these effects. Consistent with this, rats administered Ang II had increased whole body heat production and oxygen consumption. Additionally, chronic icv Ang II increased uncoupling protein-1 and ␤ 3-adrenergic receptor expression in brown adipose tissue and ␤3-adrenergic receptor expression in white adipose tissue, which is suggestive of enhanced sympathetic activation and thermogenesis. Chronic icv Ang II also increased hypothalamic agouti-related peptide and decreased hypothalamic proopiomelanocortin expression, consistent with a state of energy deficit. Moreover, chronic icv Ang II increased the anorectic corticotrophin-and thyroid-releasing hormones within the hypothalamus. These results suggest that Ang II acts in the brain to promote negative energy balance and that contributing mechanisms include an alteration in the hypothalamic circuits regulating energy balance, a decrease in food intake, an increase in energy expenditure, and an increase in sympathetic activation of brown and white adipose tissue. food intake; obesity; renin-angiotensin system MILLIONS OF PEOPLE SUFFER FROM OBESITY and the concomitant susceptibility to cardiovascular disease and type 2 diabetes, and emerging evidence has implicated the renin-angiotensin system (RAS) as contributing to these disorders; one consequence is that the RAS has emerged as a novel target for the treatment of these comorbidities (5,6,30,68,70,83). The RAS is best known as an endocrine system important in the regulation of cardiovascular function and hydromineral balance; however, recent evidence suggests that RAS also plays a substantial role in the regulation of energy and glucose homeostasis (5,6,30,68,70,83). Most physiological actions of the RAS are exerted by angiotensin II (Ang II), a peptide that is synthesized from angiotensinogen (AGT) via a series of proteolytic cleavage events. Drugs that reduce Ang II synthesis [angiotensinconverting enzyme (ACE) inhibitors] or action [angiotensin type 1 receptor blockers (ARBs)] have been used to treat hypertension for decades, and more recently, clinical and preclinical studies have explored the utility of these pharmacological agents to promote insulin sensitivity (1, 57). Interestingly, we and others have identified a potential novel utility of these pharmacological agents as therapeutics for obesity using animal models (4,16,21,76,84,85).Although interference with systemic RAS activity consistently decreases body weight and fat in rodent studie...

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MEMRI reveals altered activity in brain regions associated with anxiety, locomotion, and cardiovascular reactivity on the elevated plus maze in the WKY vs SHR rats

Zubcevic

Watkins

Pérez

et al. 2017

Brain Imaging and Behavior

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Individuals with anxiety/depression often have exaggerated cardiovascular responses to stressful stimuli and a comorbidity with hypertension. Alternatively, individuals with hypertension can be more anxious. In the present study cardiovascular changes were evaluated during behavioral testing of anxious behavior on the elevated plus maze (EPM) in the spontaneously hypertensive rat (SHR), a rodent model of neurogenic hypertension, and compared to the response of the more anxious, but normotensive, Wistar-Kyoto rat (WKY). Manganese-enhanced magnetic resonance imaging (MEMRI) was used to identify regional differences in baseline brain activity. Parallel to indicators of elevated behavioral anxiety on the EPM, WKYs had a greater increase in blood pressure but not heart rate when compared to the SHR while on the EPM. Associated with differences in anxiety-related behavior and autonomic responses, we observed increased baseline activity in the amygdala, central gray, habenula and interpeduncular nucleus with MEMRI of the WKY compared to the SHR. Conversely, elevated baseline brain activity was found in regions associated with blood pressure control and system arousal, including the hypothalamus, locus coeruleus and pedunculopontine tegmental nucleus, in the SHR vs WKY, in-line with increased resting blood pressure and increased mobility in this strain. Lastly, reduced activity in hippocampal regions was identified in the SHR compared to the WKY and may be associated with cognitive impairment previously reported in the SHR. Thus, autonomic reactivity may be a true measure of stress in rodent models of anxiety and MEMRI presents a powerful technique to uncover novel brain mechanisms of blood pressure control.

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Hypertensive effects of central angiotensin II infusion and restraint stress are reduced with age

Abstract: This study demonstrates that the role of central AngII diminishes with age in the regulation of BP both during baseline conditions and during stress, whereas the involvement of AngII in the regulation of HR remains unaffected.

Cited by 11 publications

References 41 publications

Effect of High-Salt Diet on Age-Related High Blood Pressure and Hypothalamic Redox Signaling

Effect of High-Salt Diet on Age-Related High Blood Pressure and Hypothalamic Redox Signaling

Central angiotensin II has catabolic action at white and brown adipose tissue

MEMRI reveals altered activity in brain regions associated with anxiety, locomotion, and cardiovascular reactivity on the elevated plus maze in the WKY vs SHR rats

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