Sexual dimorphism in rabbit aortic endothelial function under acute hyperglycemic conditions and gender-specific responses to acute 17β-estradiol

2008 ◽  
Vol 294 (6) ◽  
pp. H2411-H2420 ◽  
Author(s):  
Aditya Goel ◽  
Der Thor ◽  
Leigh Anderson ◽  
Roshanak Rahimian
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Rabbit Aorta ◽  
Epidemiological Data ◽  
Male And Female ◽  
Pkc Isoforms ◽  
17Β Estradiol ◽  
Pkc Β ◽  
Estrogen Administration

Epidemiological data suggest that hyperglycemia abrogates the gender-based cardiovascular protection possibly associated with estrogens. This study was designed to investigate 1) whether rabbit aortic rings show gender differences in the development of abnormal endothelium-dependent vasodilation (EDV) under acute hyperglycemic conditions, 2) the potential role of PKC isoforms and superoxide (O2−) in acute hyperglycemia-induced vascular dysfunction, and 3) the effect of acute estrogen administration on hyperglycemia-induced endothelial dysfunction in male and female rabbits. EDV to ACh was determined before and after 3 h of treatment with high glucose (HG) in phenylephrine-precontracted aortic rings from male and female New Zealand White rabbits. Similar experiments were conducted in the presence of inhibitors of PKC-α, PKC-β, and PKC-δ or an O2− scavenger. The effect of acute estrogen administration was evaluated in the presence and absence of HG. Finally, mRNA expression of PKC isoforms was measured by real-time PCR. We found that 1) 3 h of incubation with HG impairs EDV to a greater extent in female than male aorta, 2) inhibition of PKC-β or O2− prevents HG-induced impairment of EDV in female aorta, 3) acute 17β-estradiol aggravates HG-induced endothelial dysfunction in female, but not male, aorta, and 4) PKC-α and PKC-β expression are significantly higher in female than male aorta. This study reveals the predisposition of female rabbit aorta to vascular injury under hyperglycemic conditions, possibly via activation of PKC-β and O2− production. Furthermore, it suggests that, under hyperglycemic conditions, acute estrogen treatment is detrimental to endothelial function in female rabbits.

Abstract 665: Activation of Histone Deacetylase 2: A Novel Strategy for Reversing Vascular Dysfunction in Atherogenesis

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Deepesh Pandey ◽  
Gautam Sikka ◽  
Yehudis Bergman ◽  
Jae H Kim ◽  
Sungwoo Ryoo ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Cell Activation ◽  
Vascular Dysfunction ◽  
Hdac Inhibitors ◽  
Ros Production ◽  
Promoter Regions ◽  
Endothelial Cell Activation ◽  
Novel Therapy ◽  
Histone Deacetylase 2

Arginase 2 is a critical target in atherosclerosis as it regulates both endothelial NO, fibrosis and inflammation. The increase in Arg2 activity with endothelial cell activation is dependent on both early post-translational dependent mechanisms as well as a later increase in Arg 2 expression. The regulators of Arg2 transcription in the endothelium have not been characterized. The goal of current study is to determine the role of specific HDACs in the regulation of endothelial Arg2 transcription and thereby endothelial function. The global HDAC inhibitor, trichostatin (TSA) both time and concentration-dependently increased Arg2 mRNA, protein levels and activity in both HAECs and mouse aortic rings, a process that leads to Arg2-dependent endothelial dysfunction. TSA and atherogenic stimulus enhances activity of common promoter regions of Arg 2. All non-selective Class I HDAC inhibitors (TSA, Scriptaid, varinostat) enhanced Arg2 expression, while only the, the HDCA 1 and 2 selective inhibitor, mocetinostat (MGCD) enhances Arg2 expression. Overexpression of HDAC 2, 3 or 8 in HAECs have no effect on Arg 2 expression while HDAC2 cDNA overexpression concentration-dependently suppresses Arg2 expression. Conversely, siRNA knockdown of HDAC2 enhances Arg2 expression. Additionally like TSA, mouse aortic rings pre-incubated with MGCD resulted in endothelial dysfunction. Finally HDAC inhibition with TSA decreased endothelial NO and increased ROS production in an arginase-inhibitable manner. In conclusion, HDAC2 is critical regulator of Arg2 expression thereby regulating endothelial NO and ROS production, and consequently endothelial function. Overexpression or activation of HDAC2 thus represents a novel therapy for the prevention and treatment of endothelial dysfunction and atherosclerosis.

CD14+CD16++ “nonclassical” monocytes are associated with endothelial dysfunction in patients with coronary artery disease

2017 ◽  
Vol 117 (05) ◽  
pp. 971-980 ◽  
Author(s):  
Karol Urbanski ◽  
Dominik Ludew ◽  
Grzegorz Filip ◽  
Magdalena Filip ◽  
Agnieszka Sagan ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Mononuclear Cells ◽  
Vascular Dysfunction ◽  
Activation Markers ◽  
Mammary Arteries ◽  
No Bioavailability ◽  
Artery Disease

SummaryEndothelial dysfunction and inflammation are key mechanisms of vascular disease. We hypothesised that heterogeneity of monocyte subpopulations may be related to the development of vascular dysfunction in coronary artery disease (CAD). Therefore, we examined the relationships between monocyte subsets (CD14++CD16– “classical – Mon1”, CD14++CD16+ “intermediate – Mon2” and CD14+CD16++ “nonclassical – Mon3”), endothelial function and risk factor profiles in 130 patients with CAD undergoing coronary artery bypass grafting. This allowed for direct nitric oxide (NO) bioavailability assessment using isometric tension studies ex vivo (acetylcholine; ACh- and sodium- nitropruside; SNP-dependent) in segments of internal mammary arteries. The expression of CD14 and CD16 antigens and activation markers were determined in peripheral blood mononuclear cells using flow cytometry. Patients with high CD14+CD16++ “nonclassical” and low CD14++CD16- “classical” monocytes presented impaired endothelial function. High frequency of CD14+CD16++ “nonclassical” monocytes was associated with increased vascular superoxide production. Furthermore, endothelial dysfunction was associated with higher expression of activation marker CD11c selectively on CD14+CD16++ monocytes. Nonclassical and classical monocyte frequencies remained independent predictors of endothelial dysfunction when major risk factors for atherosclerosis were taken into account (β =0.18 p=0.04 and β =-0.19 p=0.03, respectively). In summary, our data indicate that CD14+CD16++ “nonclassical” monocytes are associated with more advanced vascular dysfunction measured as NO-bioavailability and vascular reactive oxygen species production.

scholarly journals Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS?

2019 ◽  
Vol 20 (15) ◽  
pp. 3775 ◽  
Author(s):  
Cesar A. Meza ◽  
Justin D. La Favor ◽  
Do-Houn Kim ◽  
Robert C. Hickner
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Enzymatic Production

NADPH oxidases (NOX) are enzyme complexes that have received much attention as key molecules in the development of vascular dysfunction. NOX have the primary function of generating reactive oxygen species (ROS), and are considered the main source of ROS production in endothelial cells. The endothelium is a thin monolayer that lines the inner surface of blood vessels, acting as a secretory organ to maintain homeostasis of blood flow. The enzymatic production of nitric oxide (NO) by endothelial NO synthase (eNOS) is critical in mediating endothelial function, and oxidative stress can cause dysregulation of eNOS and endothelial dysfunction. Insulin is a stimulus for increases in blood flow and endothelium-dependent vasodilation. However, cardiovascular disease and type 2 diabetes are characterized by poor control of the endothelial cell redox environment, with a shift toward overproduction of ROS by NOX. Studies in models of type 2 diabetes demonstrate that aberrant NOX activation contributes to uncoupling of eNOS and endothelial dysfunction. It is well-established that endothelial dysfunction precedes the onset of cardiovascular disease, therefore NOX are important molecular links between type 2 diabetes and vascular complications. The aim of the current review is to describe the normal, healthy physiological mechanisms involved in endothelial function, and highlight the central role of NOX in mediating endothelial dysfunction when glucose homeostasis is impaired.

scholarly journals Antioxidant Treatment Reverts Increased Arterial Basal Tone and Oxidative Stress in Nephrectomized (5/6) Hypertensive Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Rodrigo O. Marañón ◽  
Claudio Joo Turoni ◽  
Maria Sofia Karbiner ◽  
Nicolas Salas ◽  
Maria Peral de Bruno
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Basal Tone ◽  
No Bioavailability

Nonischemic 5/6 nephrectomized rat (NefR) is a model of chronic kidney disease. However, little is known about vascular dysfunction and its relation with hypertension in NefR.Aims. To evaluate possible alterations of endothelial function, NO-bioavailability, and basal tone in aorta from NefR and the role of oxidative stress. Sprague Dawley rats were divided into sham rats (SR), NefR, and NefR treated with tempol (NefR-T). Mean arterial pressure (MAP) and renal function were determined. In isolated aortic rings the following was measured: 1-endothelial function, 2-basal tone, 3-NO levels, 4-membrane potential (MP), and 5-oxidative stress. NefR increased MAP (SR: 119 ± 4 mmHg;n=7; NefR: 169 ± 6;n=8;P<0.001). Tempol did not modify MAP (NefR-T: 168 ± 10;n=6;P<0.001). NefR showed endothelial dysfunction, increased basal tone and decreased NO levels (SR: 32 ± 2 nA;n=7, NefR: 10 ± 2;n=8;P<0.001). In both in vitro and in vivo tempol improves basal tone, NO levels, and MP. Oxidative stress in NefR was reverted in NefR-T. We described, for the first time, that aorta from NefR presented increased basal tone related to endothelial dysfunction and decreased NO-bioavailability. The fact that tempol improves NO-contents and basal tone, without decrease MAP, indicates that oxidative stress could be implicated early and independently to hypertension, in the vascular alterations.

scholarly journals Protective effect of extracellular superoxide dismutase on endothelial function during aging

2009 ◽  
Vol 296 (6) ◽  
pp. H1920-H1925 ◽  
Author(s):  
Donald D. Lund ◽  
Yi Chu ◽  
Jordan D. Miller ◽  
Donald D. Heistad
Keyword(s):  
Superoxide Dismutase ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Ex Vivo ◽  
Vascular Dysfunction ◽  
Extracellular Superoxide Dismutase ◽  
Mrna Levels ◽  
Wild Type ◽  
Vasomotor Function ◽  
Old Mice

Endothelial vasomotor function decreases with increasing age. Extracellular superoxide dismutase (ecSOD) protects against vascular dysfunction in several disease states. The purpose of this study was to determine whether endogenous ecSOD protects against endothelial dysfunction in old mice. Vasomotor function of the aorta was studied ex vivo in wild-type (ecSOD+/+) and ecSOD-deficient (ecSOD−/−) mice at 11 (adult) and 29 (old) mo of age. Maximal relaxation to acetylcholine (10−4 M) was impaired in vessels from adult ecSOD−/− mice [75 ± 3% (mean ± SE)] compared with wild-type mice (89 ± 2%, P < 0.05). Maximal relaxation to acetylcholine (10−4 M) was profoundly impaired in aorta from old ecSOD−/− mice (45 ± 5%) compared with wild-type mice (75 ± 4%, P < 0.05). There was a significant correlation between expression of ecSOD and maximal relaxation to acetylcholine in adult and old mice. Tempol (1 mM), a scavenger of superoxide, improved relaxation in response to acetylcholine (63 ± 8%) in old ecSOD−/− mice ( P < 0.05), but not wild-type mice (75 ± 4%). Maximal relaxation to sodium nitroprusside was similar in aorta from adult and old wild-type and ecSOD−/− mice. Quantitative RT-PCR showed a decrease in mRNA levels of ecSOD and catalase in aorta of old mice and an increase in levels of TNFα and Nox-4 in aorta of old mice compared with adult mice. The findings support the hypothesis that impaired antioxidant mechanisms may contribute to cumulative increases in oxidative stress and impaired endothelial function in old mice. In conclusion, endogenous ecSOD plays an important role in protection against endothelial dysfunction during aging.

Abstract 041: Elevated Circulating Copeptin in Mid-Gestation is Associated with Increased Aortic Stiffness and Vascular Endothelial Dysfunction in Pregnant Women at High Risk for Preeclampsia

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Gary L Pierce ◽  
Donna A Santillan ◽  
Diedre Fleener ◽  
Sabrina M Scroggins ◽  
Kimberlly K Leslie ◽  
...  
Keyword(s):  
High Risk ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Pregnant Women ◽  
Brachial Artery ◽  
Aortic Stiffness ◽  
Vascular Dysfunction ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Vascular Endothelial Function

Circulating copeptin, a stable biomarker of vasopressin (AVP) secretion, is elevated throughout pregnancy in women who develop preeclampsia (PreE) and is a strong predictor of PreE as early as the 6th week gestation. Reduced vascular endothelial function and increased aortic stiffness occur in mid-gestation before clinical signs/symptoms of PreE manifest, suggesting that maternal vascular dysfunction may be an early event in the pathogenesis of PreE. However, it is unknown whether elevated copeptin/AVP in early/mid gestation contributes to vascular dysfunction in pregnant women who subsequently develop PreE. Therefore, we hypothesized that elevated copeptin would be associated with increased aortic stiffness and reduced vascular endothelial function in early/mid gestation of pregnant women at high risk for PreE. Pregnant women in the 1st trimester (n=72; age=30 ±1 yrs; BMI=34 ± 1 kg/m2) with at least 1 risk factor for PreE were enrolled. Aortic stiffness (carotid-femoral pulse wave velocity, CFPWV), vascular endothelial function (brachial artery flow-mediated dilation, FMD), blood pressure (BP) and plasma copeptin (ELISA) were assessed in both the 1st (11.7 ± 0.2 wks) and 2nd (18.8 ± 0.4 wks) trimesters. In the 1st trimester, CFPWV (7.3 ± 0.2 vs. 7.3 ± 0.5 m/sec, P=0.86), brachial artery FMD (12.9 ± 1.1 vs. 14.3 ± 2.0%, P=0.53), BP, BMI and age did not differ between women in the highest (1513 ± 221 pg/ml) vs. lowest (279 ± 12 pg/ml) quartile of copeptin (P<0.01). In contrast, 2nd trimester CFPWV was greater (7.2 ± 0.2 vs. 6.4 ± 0.2 m/sec, P<0.05) and brachial artery FMD was lower (10.2 ± 2.8 vs. 16.5 ± 1.3 %, P<0.05) among women in the highest (1714 ± 481 pg/ml) vs. the lowest (249 ± 13 pg/ml) quartile of copeptin (P<0.01), in the absence of differences in BP, BMI or age. For the entire cohort, (log)copeptin was significantly correlated with CFPWV (r=0.23, P=0.04) and tended to correlate with FMD (r=-0.23, P=0.06) in the 2nd but not in the 1st trimester. These data suggest that elevated copeptin in mid-gestation is associated with aortic stiffness and vascular endothelial dysfunction in pregnant women at high risk for PreE, but whether increased copeptin/AVP causes vascular dysfunction in pregnancies destined for PreE requires further studies using animal models.

Abstract P314: Effect of Sex on Blood Pressure and Endothelial Dysfunction in the Novel BPH2 Mouse Model of Hypertension

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Sean P Didion
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Renin Angiotensin System ◽  
Similar Degree ◽  
The Novel ◽  
Angiotensin System ◽  
Male And Female ◽  
Renin Angiotensin

Very little is known regarding blood pressure and endothelial function between the sexes in the hypertensive BPH2 mouse. Thus, the first goal was determine whether blood pressure and endothelial function are significantly different between male and female BPH2 mice. Information regarding the role of the renin-angiotensin system in the BPH2 mouse is also limited; therefore the second goal was to determine the role of the renin-angiotensin system by treating BPH2 mice with captopril for 4 weeks. Systolic blood pressure (SBP) was significantly elevated (P<0.05) and yet comparable (P>0.05) in male and female BPH2 mice and averaged 140±3 and 136±3 mmHg, respectively, whereas, in control mice SBP averaged 112±4 mmHg. Endothelial responses to acetylcholine in carotid artery were markedly impaired (P<0.05) and to a similar degree in male and female BPH2 mice as compared to controls. Captopril treatment was associated with a significant (P<0.05) reduction in blood pressure of 35±7 and 43±4 mmHg in male and female BPH2 mice, respectively. Captopril also resulted in an improvement of endothelial responses in male and female BPH2 mice. These findings demonstrate that male and female BPH2 mice are equally hypertensive and both sexes are characterized by endothelial dysfunction. In addition, the renin-angiotensin system may contribute to both hypertension and endothelial dysfunction in this model. Taken together, our data define the BPH2 mouse as an important model to compare and contrast the effects of hypertension between the sexes. Supported by NIH HL-107632.

Vascular and Endothelial Biology of Aging

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. SCI-5-SCI-5
Author(s):  
Frank M. Faraci
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Transgenic Mice ◽  
Nadph Oxidase ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Rho Kinase ◽  
Vascular Aging ◽  
Age Related ◽  
The Brain

Abstract Although aging is one of the greatest risk factors for vascular disease, very little is known regarding mechanisms that control the progression of vascular aging at the level of the endothelial cell. Endothelial dysfunction - a critical element of carotid artery and cerebrovascular disease - progresses with age, contributing to hypoperfusion, increased risk for ischemic stroke, and cognitive decline. Studies from several laboratories support the concept that age-induced endothelial dysfunction may occur earlier and be larger in magnitude in the cerebral circulation than in blood vessels outside of the brain. Thus, the circulationof the brain may be particularly sensitive to age-induced endothelial dysfunction. In relation to underlying mechanisms, angiotensin II type 1 receptors, NADPH oxidase, and oxidative stress appear to play a key role in age-related vascular dysfunction. The nuclear receptor peroxisome proliferator-activated receptor-g (PPARg) exerts protective effects in the vasculature when pharmacologically activated. We recently examined the hypothesis that endothelial PPARg protects against vascular aging. We studied carotid arteries from adult and old transgenic mice with endothelial specific expression of a human dominant negative mutation in PPARg driven by the vascular cadherin promoter (designated E-V290M), along with non-transgenic littermates. Endothelial function was similar in arteries from adult non-transgenic and E-V290M mice as well as old non-transgenic mice. In contrast, there was a marked reduction in endothelial function in old E-V290M mice. This augmented endothelial dysfunction was not altered by inhibition of cyclooxygenase, but was restored to normal by a superoxide scavenger, an inhibitor of NADPH oxidase, or inhibition of Rho kinase. Oxidant and inflammatory related mechanisms often interact. Vascular expression of interleukin-6, another mediator of vascular disease, was increased 1.6-fold in old non-transgenic mice, but almost 9-fold in old E-V290M mice. Expression of CDKN2A, a molecular marker of senescence, was ~two-fold greater in old E-V290M mice compared to controls. These findings provide the first evidence that senescence and age-related vascular dysfunction is accelerated following cell-specific interference with endothelial PPARg through mechanisms that involve oxidative stress, inflammation, and Rho kinase. This critical role for endothelial PPARg has implications for vascular pathophysiology as well as therapeutic approaches for age-induced large and small vessel disease. Disclosures No relevant conflicts of interest to declare.

scholarly journals Endothelial Dysfunction in Cystic Fibrosis: Role of Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Matthew A. Tucker ◽  
Brandon M. Fox ◽  
Nichole Seigler ◽  
Paula Rodriguez-Miguelez ◽  
Jacob Looney ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Lipid Hydroperoxide ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Vascular Endothelial Function ◽  
Artery Flow

Oxidative stress and vascular endothelial dysfunction are established characteristics of cystic fibrosis (CF). Oxidative stress may contribute to vascular dysfunction via inhibition of nitric oxide (NO) bioavailability. Purpose. To determine if ingestion of a single antioxidant cocktail (AOC) improves vascular endothelial function in patients with CF. Methods. In 18 patients with CF (age 8-39 y), brachial artery flow-mediated dilation (FMD) was assessed using a Doppler ultrasound prior to and two hours following either an AOC (n=18; 1,000 mg vitamin C, 600 IU vitamin E, and 600 mg α-lipoic acid) or a placebo (n=9). In a subgroup of patients (n=9), changes in serum concentrations of α-tocopherol and lipid hydroperoxide (LOOH) were assessed following AOC and placebo. Results. A significant (p=0.032) increase in FMD was observed following AOC (Δ1.9±3.3%), compared to no change following placebo (Δ−0.8±1.9%). Moreover, compared with placebo, AOC prevented the decrease in α-tocopherol (Δ0.48±2.91 vs. −1.98±2.32 μM, p=0.024) and tended to decrease LOOH (Δ−0.2±0.1 vs. 0.1±0.1 μM, p=0.063). Conclusions. These data demonstrate that ingestion of an antioxidant cocktail can improve vascular endothelial function and improve oxidative stress in patients with CF, providing evidence that oxidative stress is a key contributor to vascular endothelial dysfunction in CF.

scholarly journals Selective deletion of endothelial mineralocorticoid receptor protects from vascular dysfunction in sodium-restricted female mice

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jessica L. Faulkner ◽  
Emily Lluch ◽  
Simone Kennard ◽  
Galina Antonova ◽  
Iris Z. Jaffe ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Mineralocorticoid Receptor ◽  
Vascular Reactivity ◽  
Vascular Dysfunction ◽  
Comorbid Condition ◽  
Female Mice ◽  
Vascular Contractility ◽  
Aldosterone Production ◽  
Relaxation Responses

Abstract Background Recent evidence by our laboratory demonstrates that women and female mice endogenously express higher endothelial mineralocorticoid receptor (ECMR) than males. Mounting clinical evidence also indicates that aldosterone production is higher in pathological conditions in females compared to males. However, the role for increased activation of ECMR by aldosterone in the absence of a comorbid condition is yet to be explored. The current study hypothesized that increased ECMR activation induced by elevated aldosterone production predisposes healthy female mice to endothelial dysfunction. Method Vascular reactivity was assessed in aortic rings from wild-type (WT) and ECMR KO (KO) mice fed either a normal salt (NSD, 0.4% NaCl) or sodium-restricted diet (SRD, 0.05% NaCl) for 28 days. Results SRD elevated plasma aldosterone levels as well as adrenal CYP11B2 and angiotensin II type 1 receptor (AT1R) expressions in female, but not male, WT mice. In baseline conditions (NSD), endothelial function, assessed by vascular relaxation to acetylcholine, was higher while vascular contractility to phenylephrine, serotonin, and KCl lower in female than male WT mice. SRD impaired endothelial function and increased vascular contractility in female, but not male, WT mice effectively ablating the baseline sex differences. NOS inhibition with LNAME ablated endothelial relaxation to a higher extent in male than female mice on NSD and ablated differences in acetylcholine relaxation responses between NSD- and SRD-fed females, indicating a role for NO in SRD-mediated endothelial function. In association, SRD significantly reduced vascular NOX4 expression in female, but not male, mice. Lastly, selective deletion of ECMR protected female mice from SRD-mediated endothelial dysfunction and increased vascular contractility. Conclusion Collectively, these data indicate that female mice develop aldosterone-induced endothelial dysfunction via endothelial MR-mediated reductions in NO bioavailability. In addition, these data support a role for ECMR to promote vascular contractility in female mice in response to sodium restriction.

Sign in / Sign up

Export Citation Format

Share Document