Adolescent vulnerability to cardiovascular consequences of chronic emotional stress: Review and perspectives for future research

Emotional stress has been recognized as a modifiable risk factor for cardiovascular diseases. Adolescence has been proposed as a developmental period of vulnerability to stress. This idea has been mainly supported by experimental research in animals demonstrating a higher impact of chronic emotional stress in adolescents compared with adults. Adolescent vulnerability is also based on evidence that stress during this developmental period affects development, so that enduring changes are found in adult animals that experienced stress during adolescence. The purpose of the present review is to discuss experimental research in rodent models that investigated the impact of long-term exposure to stressful events during adolescence on cardiovascular function. The development of cardiovascular function and autonomic activity in rodents is initially reviewed. Then, a discussion of an adolescent vulnerability to cardiovascular effects of chronic stress is presented. From the reviewed literature, perspective for future research is proposed to better elucidate adolescent vulnerability to cardiovascular complications evoked by chronic emotional stress.     

Ontogeny of Hypothalamic Corticotropin-Releasing Factor and Anterior Pituitary Pro-opiomelanocortin Expression in Male and Female Offspring of Alcohol-Exposed and Adrenalectomized Dams

This study was designed to determine whether the previously described sexually dimorphic changes in rat hypothalamic corticotrop-in-releasing factor (CRF) and anterior pituitary pro-opiomelanocortin (POMC) mRNA expression in response to fetal alcohol exposure (FAE) are present prepubertally and whether they are altered by maternal adrenalectomy. Hypothalamic CRF and anterior pituitary POMC mRNA levels were determined in male and female offspring of adrenalectomized (ADX) and sham-adrenalectomized (Sham) dams exposed to alcohol (FAE) or a pair-fed (PF) control diet during the last 2 weeks of gestation. CRF and POMC mRNA levels were measured by Northern blotting at 1, 7, 14, and 21 days of age. In offspring of control PF dams, CRF mRNA levels increased faster in females, increasing by day 7, followed by a decrease at days 14 and 21, whereas in males there was a gradual increase from days 1 to 21. FAE altered the ontogenic profile of CRF mRNA in female offspring by delaying and exaggerating the rise of CRF expression to day 14, but produced no effect in males. Maternal adrenalectomy, combined with FAE, resulted in an early rise of CRF mRNA on day 14 in male offspring. In females, the combined ADX/FAE treatment resulted in significantly increased CRF mRNA levels, compared with those of ADX/PF offspring, on days 7 and 14. By day 21, these differences in CRF mRNA levels between the ADX/FAE and ADX/PF offspring had disappeared. POMC mRNA levels generally increased by day 7, followed by a dramatic decrease by day 14 and another increase by day 21. FAE male offspring showed decreased levels of POMC mRNA, whereas females were not affected. Maternal adrenalectomy reversed this inhibition in male offspring, resulting in POMC mRNA levels similar to those measured in male offspring of PF control animals. In contrast, POMC mRNA levels of female offspring of ADX dams decreased in response to FAE. These data suggest that the previously observed switch from suppressed to enhanced POMC expression in FAE males is the result of developmental events beyond weaning. Because this sexually dimorphic regulation of CRF and POMC expression by prenatal alcohol exposure and maternal adrenalectomy occurs before the presence of adult levels of sex steroids, this suggests an organizational effect on the developing hypothalamic-pituitary-adrenal function.     

Association between OPCRIT dimensions and polymorphisms of HPA axis genes in bipolar disorder

The aim of the study was to investigate the possible association between polymorphisms of HPA axis genes-CRHR₁ (corticotrophin-releasing hormone receptor), NR3C1 (glucocorticoid receptor) and AVPR1B (arginine vasopressin receptor) and dimensions of bipolar disorder assessed by OPCRIT.     

Ghrelin,Hypothalamus-Pituitary-Adrenal (HPA) Axis and Cushing's Syndrome

Ghrelin, a peptide predominantly produced by the stomach, has been discovered as a natural ligand of the GH Secretagogue receptor type 1a (GHS-R1a), known as specific for synthetic GHS. Ghrelin has recently attracted considerable interest as a new orexigenic factor. However, ghrelin exerts pleiotropic actions that are explained by the widespread distribution of ghrelin and GHS-R expression. Besides strong stimulation of GH secretion, the neuroendocrine ghrelin actions also include significant stimulation of both lactotroph and corticotroph secretion; all these actions depend on acylation of ghrelin in serine-3 that allows binding and activation of the GHS-R1a. However, GHS-R subtypes are likely to exist; they also bind unacylated ghrelin that is, in fact, the most abundant circulating form and exerts some biological actions. Ghrelin secretion is mainly regulated by metabolic signals, namely inhibited by feeding, glucose and insulin while stimulated by energy restriction. The role of glucocorticoids on ghrelin synthesis and secretion is still unclear although morning ghrelin levels have been found reduced in some patients with Cushing's syndrome; this, however, would simply reflect its negative association to body mass. Ghrelin, like synthetic GHS, stimulates ACTH and cortisol secretion in normal subjects and this effect is generally sensitive to the negative glucocorticoid feedback. It is remarkable that, despite hypercortisolism, ghrelin as well as synthetic GHS display marked increase in their stimulatory effect on ACTH and cortisol secretion in patients with Cushing's disease. This is even more intriguing considering that the GH response to ghrelin and GHS is markedly reduced by glucocorticoid excess. It has been demonstrated that the ACTH-releasing effect of ghrelin and GHS is purely mediated at the central level in physiological conditions; its enhancement in the presence of ACTH-secreting tumours is, instead, likely to reflect direct action on GHS receptors present on the neoplastic tissues. In fact, peculiar ACTH hyperresponsiveness to ghrelin and GHS has been observed also in ectopic ACTH-secreting tumours.     

焦虑障碍的催产素-HPA轴异常及针刺干预机理探析

新近研究发现,催产素(Oxytocin,OT)系统的激活可抑制下丘脑-垂体-肾上腺轴(hypothalamo-pituitary-adrenalaxis,HPA轴)亢进而发挥抗焦虑效应;OT-HPA轴活性异常与焦虑障碍的发生密切相关。针刺对焦虑障碍有良好的调节作用。针刺调节焦虑障碍与OT-HPA轴是否相关,尚未见文献研究与分析报道。据此,本文拟从OT、HPA轴和OT-HPA轴与焦虑障碍,以及针刺调节OT-HPA轴这四方面,分析探讨针刺治疗焦虑障碍的OT-HPA轴调节机理,从而为针刺治疗焦虑障碍的新机制研究提供思路。     

The effects of water immersion and restraint stress on the expressions of apelin,apelin receptor (APJR) and apoptosis rate in the rat heart

Apelin has been identified as an endogenous ligand of the orphan G-protein-coupled apelin receptor (APJR). These receptors are widely expressed in the central nervous system and periphery and play a role in the regulation of fluid and glucose homeostasis, feeding behavior, vessel formation, cell proliferation and immunity. We aimed to investigate whether water immersion and restraint stress have effects on apelin and APJR expression and apoptosis in heart tissue of male Wistar rats. The cardiac tissues were obtained from control, water immersion and restraint stress (WIRS) and apelin antagonist (F13A) + WIRS groups of rats and embedded in paraffin wax. Immunohistochemical staining methods were used to localize apelin, APJR and TUNEL immunopositive cells. H-SCORE was used for semi-quantitative determinations. Apelin protein levels were determined by Western blot in the cardiac tissues and plasma corticosteroid levels were measured by enzyme immunoassay (EIA). Apelin immunolocalization was found especially in endothelial cells and mast cells and faintly in cardiomyocytes, APJR immunostaining was shown in endothelial cells and cardiomyocytes, and TUNEL reaction was observed in endothelial cells and in some fibroblasts. Apelin expression was significantly increased in the WIRS and F13A + WIRS groups compared to the control group. The APJR reaction was similar in all groups. The number of TUNEL-positive cells was significantly higher in the F13A + WIRS group than that of the control group. Our study showed that WIRS for 6 h increased plasma corticosterone levels and cardiac apelin expression in rats. The increased levels of apelin inhibited stress-induced apoptosis in heart. These results may be important for the therapeutic approach to a variety of stress-related heart disease.