Insufficient activation of adrenocortical but not adrenomedullary hormones during stress in rats subjected to repeated immune challenge

Moncek, Fedor; Aguilera, Greti; Ježová, Daniela

doi:10.1016/s0165-5728(03)00268-6

Cited by 19 publications

(7 citation statements)

References 44 publications

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“…In addition to acute inflammatory response, LPS activates the HPA axis, a classical hormonal response which includes enhanced hypothalamic corticotropin-releasing factor (CRF) formation and release, followed by increased adrenocorticotropic releasing hormone (ACTH) release from the pituitary gland, leading to augmented release of anti-inflammatory glucocorticoids and pro-inflammatory mineralocorticoids from the adrenal gland (Grinevich et al 2001; Moncek et al 2003). Besides regulating the HPA axis activity, LPS acts directly on the adrenal gland to enhance cyclooxygenase-2 (COX-2) activity leading to the stimulation of local inflammatory processes and glucocorticoid release (Cover et al 2001; Ichitani et al 2001; Vakharia and Hinson 2005).…”

Section: Arbs Reduce the Peripheral Innate Immune Response To Bacterimentioning

confidence: 99%

Anti-Inflammatory Effects of Angiotensin Receptor Blockers in the Brain and the Periphery

et al. 2009

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SUMMARYIn addition to regulating blood pressure, Angiotensin II exerts powerful pro-inflammatory effects in hypertension through stimulation of its AT 1 receptors, most clearly demonstrated in peripheral arteries and in the cerebral vasculature. Administration of Angiotensin II receptor blockers (ARBs) decreases hypertension-related vascular inflammation in peripheral organs. In rodent models of genetic hypertension, ARBs reverse the inflammation in the cerebral microcirculation.We hypothesized that ARBs could be effective in inflammatory conditions beyond hypertension. Our more recent studies, summarized here, indicate that this is indeed the case.We used the model of systemic administration of the bacterial endotoxin lipopolysaccharide (LPS). LPS produces a robust initial inflammatory reaction, the innate immune response, in peripheral organs and in the brain. Pretreatment with the ARB candesartan significantly diminishes the response to LPS, including reduction of pro-inflammatory cytokine release to the general circulation and decreased production and release of the pro-inflammatory adrenal hormone aldosterone. In addition, the ARB very significantly decreased the LPS-induced gene expression of pro-inflammatory cytokines and microglia activation in the brain. Our results demonstrate that AT 1 receptor activity is essential for the unrestricted development of full-scale innate immune response in the periphery and in the brain. ARBs, due to their immune response-limiting properties, may be considered as therapeutically useful in a number of inflammatory diseases of the peripheral organs and the brain.

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Section: Arbs Reduce the Peripheral Innate Immune Response To Bacterimentioning

confidence: 99%

Anti-Inflammatory Effects of Angiotensin Receptor Blockers in the Brain and the Periphery

et al. 2009

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“…Together with glucocorticoids, aldosterone is released from the adrenal cortex in response to several stress stimuli [2]. Stimulation of aldosterone release by acute and chronic stressors is mediated by angiotensin II and adrenocorticotropic hormone (ACTH) [3], [4].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Stress-Induced Changes in Adults and Pups: Is Aldosterone the Main Adrenocortical Stress Hormone during the Perinatal Period in Rats?

et al. 2013

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Positive developmental impact of low stress-induced glucocorticoid levels in early development has been recognized for a long time, while possible involvement of mineralocorticoids in the stress response during the perinatal period has been neglected. The present study aimed at verifying the hypothesis that balance between stress-induced glucocorticoid and mineralocorticoid levels is changing during postnatal development. Hormone responses to two different stressors (insulin-induced hypoglycaemia and immune challenge induced by bacterial lipopolysaccharid) measured in 10-day-old rats were compared to those in adults. In pups corticosterone responses to both stressors were significantly lower than in adults, which corresponded well with the stress hyporesponsive period. Importantly, stress-induced elevations in aldosterone concentration were significantly higher in pups compared both to corticosterone elevations and to those in adulthood with comparable adrenocorticotropin concentrations in the two age groups. Greater importance of mineralocorticoids compared to glucocorticoids in postnatal period is further supported by changes in gene expression and protein levels of gluco- (GR) and mineralocorticoid receptors (MR) and selected enzymes measured by quantitative PCR and immunohystochemistry in the hypothalamus, hippocampus, prefrontal cortex, liver and kidney. Gene expression of 11beta-hydroxysteroid dehydrogenase 2 (11β-HSD2), an enzyme enabling preferential effects of aldosterone on mineralocorticoid receptors, was higher in 10-day-old pups compared to adult animals. On the contrary, the expression and protein levels of GR, MR and 11β-HSD1 were decreased. Presented results clearly show higher stress-induced release of aldosterone in pups compared to adults and strongly suggest greater importance of mineralocorticoids compared to glucocorticoids in stress during the postnatal period.

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“…This is accompanied by a classical stress response characterized by activation of the hypothalamic-pituitary-adrenal (HPA) axis (Beishuizen and Thijs, 2004; Hopkins, 2007). During HPA axis activation, there is enhanced synthesis and release of hypothalamic corticotrophin-releasing factor (CRF) followed by an increase in pituitary ACTH formation and release, leading to augmented adrenal pro-inflammatory mineralocorticoid and anti-inflammatory glucocorticoid secretion (Elenkov and Chrousos, 2006; Fernandes et al, 2008; Grinevich et al, 2001; Moncek et al, 2003). …”

Section: Introductionmentioning

confidence: 99%

In vivo Angiotensin II AT1 receptor blockade selectively inhibits LPS-induced innate immune response and ACTH release in rat pituitary gland

Sánchez-Lemus¹,

Benický²,

Pavel³

et al. 2009

Brain, Behavior, and Immunity

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Systemic lipopolysaccharide (LPS) administration induces an innate immune response and stimulates the hypothalamic-pituitary-adrenal axis. We studied Angiotensin II AT1 receptor participation in the LPS effects with focus on the pituitary gland. LPS (50 μg/kg, i.p.) enhanced, 3 hours after administration, gene expression of pituitary CD14 and that of Angiotensin II AT1A receptors in pituitary and hypothalamic paraventricular nucleus (PVN); stimulated ACTH and corticosterone release; decreased pituitary CRF1 receptor mRNA and increased all plasma and pituitary pro-inflammatory factors studied. The AT1 receptor blocker (ARB) candesartan (1 mg/kg/day, s.c. daily for 3 days before LPS) blocked pituitary and PVN AT1 receptors, inhibited LPS-induced ACTH but not corticosterone secretion and decreased LPS-induced release of TNF-α, IL-1β and IL-6 to the circulation. The ARB reduced LPS-induced pituitary gene expression of IL-6, LIF, iNOS, COX-2 and IκB-α; and prevented LPS-induced increase of nNOS/eNOS activity. The ARB did not affect LPS-induced TNF-α and IL-1β gene expression, IL-6 or IL-1βprotein content or LPS-induced decrease of CRF1 receptors. When administered alone, the ARB increased basal plasma corticosterone levels and basal PGE2 mRNA in pituitary. Our results demonstrate that the pituitary gland is a target for systemically administered LPS. AT1 receptor activity is necessary for the complete pituitary response to LPS and is limited to specific pro-inflammatory pathways. There is a complementary and complex influence of the PVN and circulating cytokines on the initial pituitary response to LPS. Our findings support the proposal that ARBs may be considered for the treatment of inflammatory conditions.

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Insufficient activation of adrenocortical but not adrenomedullary hormones during stress in rats subjected to repeated immune challenge

Cited by 19 publications

References 44 publications

Anti-Inflammatory Effects of Angiotensin Receptor Blockers in the Brain and the Periphery

Anti-Inflammatory Effects of Angiotensin Receptor Blockers in the Brain and the Periphery

Comparison of Stress-Induced Changes in Adults and Pups: Is Aldosterone the Main Adrenocortical Stress Hormone during the Perinatal Period in Rats?

In vivo Angiotensin II AT1 receptor blockade selectively inhibits LPS-induced innate immune response and ACTH release in rat pituitary gland

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