Gonadal hormone receptors underlie the resistance of female rats to inflammatory and cardiovascular complications of endotoxemia

El-Lakany, Mohammed A.; Fouda, Mohamed A.; El‐Gowelli, Hanan M.; El‐Gowilly, Sahar M.; El‐Mas, Mahmoud M.

doi:10.1016/j.ejphar.2018.01.051

Cited by 25 publications

(22 citation statements)

References 58 publications

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“…These harmful derangements could be related to the excessive generation of inflammatory cytokines, which induce mitochondrial damage, cripple calcium homeostasis, and perturb the neuroautonomic tone (Flierl et al, 2008). We and others have previously reported sexual dimorphism in immune response to endotoxemia, with females experiencing less adverse clinical outcomes than age-matched males (Saia et al, 2015;Klein and Flanagan, 2016;El-Lakany et al, 2018).…”

Section: Introductionmentioning

confidence: 98%

Pre-eclamptic Fetal Programming Alters Neuroinflammatory and Cardiovascular Consequences of Endotoxemia in Sex-Specific Manners

Abuiessa

Wedn

El‐Gowilly

et al. 2020

J Pharmacol Exp Ther

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Pre-eclampsia (PE)-induced fetal programming predisposes offspring to health hazards in adult life. Here, we tested the hypothesis that pre-eclamptic fetal programming elicits sexually dimorphic inflammatory and cardiovascular complications to endotoxemia in adult rat offspring. PE was induced by oral administration of L-NAME (50 mg/kg per day for seven consecutive days) starting from day 14 of conception. Cardiovascular studies were performed in conscious adult male and female offspring preinstrumented with femoral indwelling catheters. Compared with non-PE male counterparts, intravenous administration of lipopolysaccharide (LPS, 5 mg/kg) to PE male offspring caused significantly greater 1) falls in blood pressure, 2) increases in heart rate, 3) rises in arterial dP/dtmax, a correlate of left ventricular contractility, and 4) decreases in time-and frequency-domain indices of heart rate variability (HRV). By contrast, the hypotensive and tachycardic actions of LPS in female offspring were independent of the pre-eclamptic state and no clear changes in HRV or dP/dtmax were noted. Measurement of arterial baroreflex activity by vasoactive method revealed no sex specificity in baroreflex dysfunction induced by LPS. Immunohistochemical studies showed increased protein expression of toll-like receptor 4 in heart as well as in brainstem neuronal pools of the nucleus of solitary tract and rostral ventrolateral medulla in endotoxic PE male, but not female, offspring. Enhanced myocardial, but not neuronal, expression of monocyte chemoattractant protein-1 was also demonstrated in LPS-treated male offspring. Together, pre-eclamptic fetal programming aggravates endotoxic manifestations of hypotension and autonomic dysfunction in male offspring via exacerbating myocardial and neuromedullary inflammatory pathways. SIGNIFICANCE STATEMENTCurrent molecular and neuroanatomical evidence highlights a key role for pre-eclamptic fetal programming in offspring predisposition to health hazards induced by endotoxemia in adult life. Pre-eclampsia accentuates endotoxic manifestations of hypotension, tachycardia, and cardiac autonomic dysfunction in male offspring via exacerbating myocardial and central inflammatory pathways. The absence of such detrimental effects in female littermates suggests sexual dimorphism in the interaction of pre-eclamptic fetal programming with endotoxemia.

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Section: Introductionmentioning

confidence: 98%

Pre-eclamptic Fetal Programming Alters Neuroinflammatory and Cardiovascular Consequences of Endotoxemia in Sex-Specific Manners

Abuiessa

Wedn

El‐Gowilly

et al. 2020

J Pharmacol Exp Ther

Self Cite

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“…This might be due in part to the high prevalence of morbidities and procedures in our unit that elevate HRC scores thus limiting their utility. In addition, HRC is known to vary with factors such as age, gender, medications, and mechanical ventilation [17][18][19][20]. Nevertheless, a tighter protocol regarding the action towards patients with increasing scores might clarify the utility of HRC monitoring in early identification of infections in our NICU patients.…”

Section: Discussionmentioning

confidence: 99%

Heart Rate Characteristic Index Monitoring for Early Detection of Infections in Very Low Birth Weight Infants

Moreira¹,

Melton²,

Meinzen‐Derr³

et al. 2019

AJP

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The aim of this study is 1) to determine the sensitivity and specificity of continuous heart rate characteristics (HRC) monitoring in detection of infections and 2) to evaluate whether HRC monitoring detects infections prior to onset of clinical symptoms in very low birth weight (VLBW) infants. A retrospective cohort study was conducted analyzing HRC scores and episodes of infection for VLBW infants in the Neonatal Intensive Care Unit (NICU) at Cincinnati Children's Hospital Medical Center from January 2015 through May 2016. HRC scores were acquired using the HRC monitor system and entered into the electronic medical record by bedside staff. Culture-positive and culture-negative clinical infections were recorded. Positive HRC scores were defined as an increase 1 point above the baseline or the first rise above 2. HRC scores within 24 hours and also within the 5-day period before the start of antibiotics for infections were analyzed for sensitivity, specificity, positive predictive value and negative predictive value for detection of neonatal infection. The HRC score increase 1 point above the baseline or the first rise above 2 in the 24 hours before the start of antibiotics for infectious events had a sensitivity of 68.0%, a specificity of 10.8%. Positive predictive value (PPV) and negative predictive value (NPV) were 34.0% and 33.3%, respectively. The PPV and NPV were modestly higher for elevated HRC scores during the 5-day period before infections, 41.1% and 66.7%, respectively. In our single-center retrospective study, elevated HRC scores had limited ability to detect infection. More than half of the positive monitor events were not related to infection. The potential clinical impact of the monitor to detect infection before the onset of clinical symptoms was limited and the risk for unnecessary evaluation and treatment was high.

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“…Animal studies have shown sexual dimorphism in the immune response to sepsis. Described are: the role of female gonadal hormones and their receptors in compensating for cardiovascular disorders induced by endotoxemia in rats [ 128 ], beneficial effects of estradiol on phagocytic and bactericidal function of immune cells [ 129 ], and estrogen-driven, innate antibody-mediated immunological strategy conferred protection providing protection against Escherichia coli in female rats [ 130 ]. This sexual dimorphism may be due to the pro-inflammatory effect of estradiol in women and the suppressive effect of testosterone on the immune system in men [ 131 ].…”

Section: Endocrine Disorders In the Course Of Sepsismentioning

confidence: 99%

Sepsis as a Pan-Endocrine Illness—Endocrine Disorders in Septic Patients

Wasyluk

Zwolak

2021

JCM

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Sepsis is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection”. One of the elements of dysregulated host response is an endocrine system disorder. Changes in its functioning in the course of sepsis affect almost all hormonal axes. In sepsis, a function disturbance of the hypothalamic–pituitary–adrenal axis has been described, in the range of which the most important seems to be hypercortisolemia in the acute phase. Imbalance in the hypothalamic–pituitary–thyroid axis is also described. The most typical manifestation is a triiodothyronine concentration decrease and reverse triiodothyronine concentration increase. In the somatotropic axis, a change in the secretion pattern of growth hormone and peripheral resistance to this hormone has been described. In the hypothalamic–pituitary–gonadal axis, the reduction in testosterone concentration in men and the stress-induced “hypothalamic amenorrhea” in women have been described. Catecholamine and β-adrenergic stimulation disorders have also been reported. Disorders in the endocrine system are part of the “dysregulated host response to infection”. They may also affect other components of this dysregulated response, such as metabolism. Hormonal changes occurring in the course of sepsis require further research, not only in order to explore their potential significance in therapy, but also due to their promising prognostic value.

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Gonadal hormone receptors underlie the resistance of female rats to inflammatory and cardiovascular complications of endotoxemia

Cited by 25 publications

References 58 publications

Pre-eclamptic Fetal Programming Alters Neuroinflammatory and Cardiovascular Consequences of Endotoxemia in Sex-Specific Manners

Pre-eclamptic Fetal Programming Alters Neuroinflammatory and Cardiovascular Consequences of Endotoxemia in Sex-Specific Manners

Heart Rate Characteristic Index Monitoring for Early Detection of Infections in Very Low Birth Weight Infants

Sepsis as a Pan-Endocrine Illness—Endocrine Disorders in Septic Patients

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