scholarly journals Protection from chronic stress- and depressive symptom-induced vascular endothelial dysfunction in female rats is abolished by preexisting metabolic disease

2018 ◽  
Vol 314 (5) ◽  
pp. H1085-H1097 ◽  
Author(s):  
Steven D. Brooks ◽  
Stanley M. Hileman ◽  
Paul D. Chantler ◽  
Samantha A. Milde ◽  
Kent A. Lemaster ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Metabolic Syndrome ◽  
Depressive Symptoms ◽  
Chronic Stress ◽  
Vascular Function ◽  
Clinical Depression ◽  
Female Rats ◽  
Zucker Rats ◽  
Vascular Protection ◽  
The Impact

While it is known that chronic stress and clinical depression are powerful predictors of poor cardiovascular outcomes, recent clinical evidence has identified correlations between the development of metabolic disease and depressive symptoms, creating a combined condition of severely elevated cardiovascular disease risk. In this study, we used the obese Zucker rat (OZRs) and the unpredictable chronic mild stress (UCMS) model to determine the impact of preexisting metabolic disease on the relationship between chronic stress/depressive symptoms and vascular function. Additionally, we determined the impact of metabolic syndrome on sex-based protection from chronic stress/depressive effects on vascular function in female lean Zucker rats (LZRs). In general, vasodilator reactivity was attenuated under control conditions in OZRs compared with LZRs. Although still impaired, conduit arterial and resistance arteriolar dilator reactivity under control conditions in female OZRs was superior to that in male or ovariectomized (OVX) female OZRs, largely because of better maintenance of vascular nitric oxide and prostacyclin levels. However, imposition of metabolic syndrome in combination with UCMS in OZRs further impaired dilator reactivity in both vessel subtypes to a similarly severe extent and abolished any protective effect in female rats compared with male or OVX female rats. The loss of vascular protection in female OZRs with UCMS was reflected in vasodilator metabolite levels, which closely matched those in male and OVX female OZRs subjected to UCMS. These results suggest that presentation of metabolic disease in combination with depressive symptoms can overwhelm the vasoprotection identified in female rats and, thereby, may reflect a severe impairment to normal endothelial function. NEW & NOTEWORTHY This study addresses the protection from chronic stress- and depression-induced vascular dysfunction identified in female compared with male or ovariectomized female rats. We determined the impact of preexisting metabolic disease, a frequent comorbidity of clinical depression in humans, on that vascular protection. With preexisting metabolic syndrome, female rats lost all protection from chronic stress/depressive symptoms and became phenotypically similar to male and ovariectomized female rats, with comparably poor vasoactive dilator metabolite profiles.

scholarly journals Metabolic Syndrome Eliminates Vascular Protection Against Chronic Stress in Female Rats

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Shyla Stanley ◽  
Steven Brooks ◽  
Camille Leon ◽  
Alex d'Audiffret ◽  
Jeff Frisbee
Keyword(s):  
Metabolic Syndrome ◽  
Chronic Stress ◽  
Female Rats ◽  
Vascular Protection

scholarly journals Integration of skeletal muscle resistance arteriolar reactivity for perfusion responses in the metabolic syndrome

2009 ◽  
Vol 296 (6) ◽  
pp. R1771-R1782 ◽  
Author(s):  
Jefferson C. Frisbee ◽  
John M. Hollander ◽  
Robert W. Brock ◽  
Han-Gang Yu ◽  
Matthew A. Boegehold
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Vascular Reactivity ◽  
Oxidant Stress ◽  
Zucker Rats ◽  
Minimal Effect ◽  
Metabolic Demand ◽  
The Metabolic Syndrome ◽  
The Impact

Previous study suggests that with evolution of the metabolic syndrome, patterns of arteriolar reactivity are profoundly altered and may constrain functional hyperemia. This study investigated interactions between parameters of vascular reactivity at two levels of resistance arterioles in obese Zucker rats (OZR), translating these observations into perfusion regulation for in situ skeletal muscle. Dilation of isolated and in situ resistance arterioles from OZR to acetylcholine, arachidonic acid (AA), and hypoxia (isolated arterioles only) were blunted vs. lean Zucker rats (LZR), although dilation to adenosine was intact. Increased adrenergic tone (phenylephrine) or intralumenal pressure (ILP) impaired dilation in both strains (OZR>LZR). Treatment of OZR arterioles with Tempol (superoxide dismutase mimetic) or SQ-29548 (prostaglandin H2/thromboxane A2 receptor antagonist) improved dilator reactivity under control conditions and with increased ILP, but had minimal effect with increased adrenergic tone. Arteriolar dilation to adenosine was well maintained in both strains under all conditions. For in situ cremasteric arterioles, muscle contraction-induced elevations in metabolic demand elicited arteriolar dilations and hyperemic responses that were blunted in OZR vs. LZR, although distal parallel arterioles were characterized by heterogeneous dilator and perfusion responses. α-Adrenoreceptor blockade improved outcomes at rest but had minimal effect with elevated metabolic demand. Treatment with Tempol or SQ-29548 had minimal impact at rest, but lessened distal arteriolar perfusion heterogeneity with increased metabolic demand. In blood-perfused gastrocnemius of OZR, perfusion was constrained primarily by adrenergic tone, while myogenic activation and endothelium-dependent dilation did not appear to contribute significantly to ischemia. These results of this novel, integrated approach suggest that adrenergic tone and metabolic dilation are robust determinants of bulk perfusion to skeletal muscle of OZR, while endothelial dysfunction may more strongly regulate perfusion distribution homogeneity via the impact of oxidant stress and AA metabolism.

scholarly journals Protective effect of sex on chronic stress- and depressive behavior-induced vascular dysfunction in BALB/cJ mice

2014 ◽  
Vol 117 (9) ◽  
pp. 959-970 ◽  
Author(s):  
Shyla C. Stanley ◽  
Steven D. Brooks ◽  
Joshua T. Butcher ◽  
Alexandre C. d'Audiffret ◽  
Stephanie J. Frisbee ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Depressive Symptom ◽  
Chronic Stress ◽  
Symptom Severity ◽  
Plasma Cortisol ◽  
Depressive Disorders ◽  
Subsequent Development ◽  
Female Rats ◽  
Mild Stress ◽  
Depressive Symptom Severity

The presence of chronic, unresolvable stresses leads to negative health outcomes, including development of clinical depression/depressive disorders, with outcome severity being correlated with depressive symptom severity. One of the major outcomes associated with chronic stress and depression is the development of cardiovascular disease (CVD) and an elevated CVD risk profile. However, in epidemiological research, sex disparities are evident, with premenopausal women suffering from depressive symptoms more acutely than men, but also demonstrating a relative protection from the onset of CVD. Given this, we investigated the differential effect of sex on conduit artery and resistance arteriolar function in male and female mice following 8 wk of an unpredictable chronic mild stress (UCMS) protocol. In males, plasma cortisol and depressive symptom severity (e.g., coat status, anhedonia, delayed grooming) were elevated by UCMS. Endothelium-dependent dilation to methacholine/acetylcholine was impaired in conduit arteries and skeletal muscle arterioles, suggesting a severe loss of nitric oxide bioavailability and increased production of thromboxane A2 vs. prostaglandin I2 associated with elevated reactive oxygen species (ROS) and an increased level of systemic inflammation. Endothelium-independent dilation was intact. In females, depressive symptoms and plasma cortisol increases were more severe than in males, although alterations to vascular reactivity were blunted, including the effects of elevated ROS and inflammation on dilator responses. These results suggest that compared with males, female rats are more susceptible to chronic stress in terms of the severity of depressive behaviors, but that the subsequent development of vasculopathy is blunted owing to an improved ability to tolerate elevated ROS and systemic inflammatory stress.

scholarly journals The impact of metabolic syndrome on mental health-related quality of life and depressive symptoms

2020 ◽  
Vol 29 (8) ◽  
pp. 2063-2072
Author(s):  
Victoria M. Limon ◽  
Miryoung Lee ◽  
Brandon Gonzalez ◽  
Audrey C. Choh ◽  
Stefan A. Czerwinski
Keyword(s):  
Quality Of Life ◽  
Mental Health ◽  
Metabolic Syndrome ◽  
Depressive Symptoms ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related ◽  
The Impact

scholarly journals Impaired HSP70 Expression in the Aorta of Female Rats: A Novel Insight Into Sex-Specific Differences in Vascular Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Amanda Almeida de Oliveira ◽  
Fernanda Priviero ◽  
R. Clinton Webb ◽  
Kenia Pedrosa Nunes
Keyword(s):  
Vascular Function ◽  
Vascular Diseases ◽  
Female Rats ◽  
Hsp70 Expression ◽  
Adrenergic Stimulation ◽  
Vascular Contraction ◽  
Vascular Responses ◽  
Cardio Vascular ◽  
Sex Disparity ◽  
The Impact

Heat-shock protein 70 (HSP70) contributes to cellular calcium (Ca2+) handling mechanisms during receptor-mediated vascular contraction. Interestingly, previous studies have independently reported sex-related differences in HSP70 expression and Ca2+ dynamics. Still, it is unknown if sex, as a variable, plays a role in the impact that HSP70 has upon vascular contraction. To narrow this gap, we investigated if differences exist in the expression levels of HSP70 in the aorta, and if targeting this protein contributes to sex disparity in vascular responses. We report that, compared with male animals, female rats present a reduction in the basal levels of HSP70. More compelling, we found that the blockade of HSP70 has a greater impact on phenylephrine-induced phasic and tonic vascular contraction in female animals. In fact, it seems that the inhibition of HSP70 significantly affects vascular Ca2+ handling mechanisms in females, which could be associated with the fact that these animals have impaired HSP70 expression. Corroborating this idea, we uncovered that the higher sensitivity of female rats to HSP70 inhibition does not involve an increase in NO-dependent vasodilation nor a decrease in vascular oxidative stress. In summary, our findings reveal a novel mechanism associated with sex-specific differences in vascular responses to α-1 adrenergic stimulation, which might contribute to unraveling the network of intertwined pathways conferring female protection to (cardio)vascular diseases.

scholarly journals Protection from vascular dysfunction in female rats with chronic stress and depressive symptoms

2018 ◽  
Vol 314 (5) ◽  
pp. H1070-H1084 ◽  
Author(s):  
Steven D. Brooks ◽  
Stanley M. Hileman ◽  
Paul D. Chantler ◽  
Samantha A. Milde ◽  
Kent A. Lemaster ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Depressive Symptom ◽  
Chronic Stress ◽  
Symptom Severity ◽  
Vascular Reactivity ◽  
Vascular Dysfunction ◽  
Sex Hormone ◽  
Female Rats ◽  
Depressive Symptom Severity ◽  
Female Subjects

The increasing prevalence and severity of clinical depression are strongly correlated with vascular disease risk, creating a comorbid condition with poor outcomes but demonstrating a sexual disparity whereby female subjects are at lower risk than male subjects for subsequent cardiovascular events. To determine the potential mechanisms responsible for this protection against stress/depression-induced vasculopathy in female subjects, we exposed male, intact female, and ovariectomized (OVX) female lean Zucker rats to the unpredictable chronic mild stress (UCMS) model for 8 wk and determined depressive symptom severity, vascular reactivity in ex vivo aortic rings and middle cerebral arteries (MCA), and the profile of major metabolites regulating vascular tone. While all groups exhibited severe depressive behaviors from UCMS, severity was significantly greater in female rats than male or OVX female rats. In all groups, endothelium-dependent dilation was depressed in aortic rings and MCAs, although myogenic activation and vascular (MCA) stiffness were not impacted. Higher-resolution results from pharmacological and biochemical assays suggested that vasoactive metabolite profiles were better maintained in female rats with normal gonadal sex steroids than male or OVX female rats, despite increased depressive symptom severity (i.e., higher nitric oxide and prostacyclin and lower H2O2and thromboxane A2levels). These results suggest that female rats exhibit more severe depressive behaviors with UCMS but are partially protected from the vasculopathy that afflicts male rats and female rats lacking normal sex hormone profiles. Determining how female sex hormones afford partial vascular protection from chronic stress and depression is a necessary step for addressing the burden of these conditions on cardiovascular health.NEW & NOTEWORTHY This study used a translationally relevant model for chronic stress and elevated depressive symptoms to determine how these factors impact conduit and resistance arteriolar function in otherwise healthy rats. While chronic stress leads to an impaired vascular reactivity associated with elevated oxidant stress, inflammation, and reduced metabolite levels, we demonstrated partial protection from vascular dysfunction in female rats with normal sex hormone profiles compared with male or ovariectomized female rats.

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