scholarly journals Baroreceptor denervation reduces inflammatory status and worsens cardiovascular collapse during systemic inflammation

2019 ◽  
Author(s):  
Mateus R. Amorim ◽  
Júnia L. de Deus ◽  
Camila A. Pereira ◽  
Luiz E. V. da Silva ◽  
Gabriela S. Borges ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Vessels ◽  
Inflammatory Cytokines ◽  
Systemic Inflammation ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Cardiovascular Collapse ◽  
Inflammatory Status ◽  
Resistance Vessels ◽  
Autonomic Cardiovascular Control

ABSTRACTBeyond the regulation of cardiovascular function, baroreceptor afferents play polymodal roles. We hypothesized that baroreceptor denervation affects lipopolysaccharide (LPS)-induced systemic inflammation (SI) and hemodynamic collapse in conscious rats, and that these parameters are interconnected. We combine: a) hemodynamic and thermoregulatory recordings after LPS administration at a septic-like dose b) analysis of the cardiovascular complexity, c) evaluation of vascular function in mesenteric resistance vessels, and d) measurements of inflammatory cytokines (plasma and spleen). LPS-induced drop in blood pressure was higher in sino-aortic denervated (SAD) rats. LPS-induced hemodynamic collapse was associated with SAD-dependent autonomic disbalance. LPS-induced vascular dysfunction was not affected by SAD. Surprisingly, SAD blunted LPS-induced surges of plasma and spleen cytokines. These data indicate that sino-aortic afferents are key to alleviate LPS-induced cardiovascular collapse, affecting the autonomic cardiovascular control, without affecting resistance blood vessels. Moreover, baroreflex modulation of the LPS-induced SI and hemodynamic collapse seem not to be interconnected.

Abstract P006: Liraglutide Attenuates Cardiac Fibrosis and Vascular Dysfunction in a Non-diabetic Angiotensin II-infusion Model via Anti-inflammatory and Anti-oxidant Mechanisms

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Huey Wen Lee ◽  
Melita Brdar ◽  
Robert Widdop ◽  
Anthony Dear ◽  
Tracey Gaspari
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Cardiac Fibrosis ◽  
Vascular Dysfunction ◽  
Cardiomyocyte Hypertrophy ◽  
High Dose ◽  
Protective Effects ◽  
Ang Ii ◽  
Treatment Protocols ◽  
Glucose Levels

Glucagon-like peptide-1 (GLP-1) based therapies are used to treat type II diabetes via increasing insulin secretion and inhibiting glucagon production. Recent evidence suggests that activating the GLP-1 receptor may also mediate direct vaso-protective effects. Therefore the objective of the study was to determine whether GLP-1R stimulation conferred cardio- and vaso-protection in a non-diabetic setting using the angiotensin (Ang) II infusion model of hypertension and cardiovascular dysfunction. Male C57Bl/6J mice (4-6 months) were assigned to one of the following 4 week treatment protocols: 1) vehicle (saline), 2) Ang II (800ng/kg/day), 3) Ang II + liraglutide (30μg/kg/day), 4) Ang II + liraglutide (300μg/kg/day). All treatments were administered via osmotic mini-pumps (s.c). After 4 weeks the effect of liraglutide treatment on blood pressure, vascular function and cardiac remodelling was examined. Liraglutide (both doses) attenuated Ang II-induced increase in systolic blood pressure (Ang II: 175.3 ± 8.6mmHg vs Ang II+Lirag (30) 150.2 ± 6.4 mmHg or Ang II+Lirag (300): 145.4 ± 6.9 mmHg) without affecting blood glucose levels. Liraglutide (both doses) completely prevented Ang II-induced endothelial dysfunction (% maximum relaxation: Ang II=50.7 ± 7.8%; Ang II+Lirag (30)=82.7 ± 5.8; Ang II+Lirag (300)=81.5 ± 6.1%). In the heart, liraglutide prevented Ang II-induced cardiomyocyte hypertrophy (n=7-10; p<0.05) and reduced collagen deposition (% collagen expression: Ang II=4.4 ± 0.5 vs Ang II+Lirag(300)=2.9 ± 0.3; n=7-9; p<0.01). This anti-fibrotic effect was attributed to reduced fibroblast/myofibroblast expression as well as decreased inflammation with reduced NFκB and MCP-1 expression and decreased oxidative stress with a significant reduction in superoxide production using high dose of liraglutide. Overall, stimulation of GLP-1R in a non-diabetic setting protected against Ang II-mediated cardiac hypertrophy, cardiac fibrosis and vascular dysfunction, indicating potential for use of GLP-1 based therapies in treatment of cardiovascular disease independent of diabetes.

Abstract 310: Deoxycorticosterone Acetate (doca)-salt Exacerbates Hypertension and Vascular Dysfunction in Mice Expressing Dominant Negative Peroxisome Proliferator-activated Receptor-gamma (pparg) in Smooth Muscle

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Pimonrat Ketsawatsomkron ◽  
Deborah R Davis ◽  
Aline M Hilzendeger ◽  
Justin L Grobe ◽  
Curt D Sigmund
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Transgenic Mice ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Critical Role ◽  
Surrogate Marker ◽  
Dominant Negative ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

PPARG, a ligand-activated transcription factor plays a critical role in the regulation of blood pressure and vascular function. We hypothesized that smooth muscle cell (SMC) PPARG protects against hypertension (HT) and resistance vessel dysfunction. Transgenic mice expressing dominant negative PPARG (S-P467L) in SMC or non-transgenic controls (NT) were implanted with DOCA pellet and allowed ad libitum access to 0.15 M NaCl for 21 days in addition to regular chow and water. Blood pressure was monitored by telemetry and mesenteric arterial (MA) function was assessed by pressurized myograph. At baseline, 24-hour mean arterial pressure (MAP) was similar between NT and S-P467L mice, while the transgenic mice were tachycardic. DOCA-salt increased MAP to a much greater degree in S-P467L mice (Δ MAP; S-P467L: +34.2±6.0, NT: +13.3±5.7, p<0.05 vs NT). Heart rate was similarly decreased in both groups after DOCA-salt. Vasoconstriction to KCl, phenylephrine and endothelin-1 did not differ in MA from DOCA-salt treated NT and S-P467L, while the response to vasopressin was significantly reduced in S-P467L after DOCA-salt (% constriction at 10-8 M, S-P467L: 31.6±5.6, NT: 46.7±3.8, p<0.05 vs NT). Urinary copeptin, a surrogate marker for arginine vasopressin was similar in both groups regardless of treatment. Vasorelaxation to acetylcholine was slightly impaired in S-P467L MA compared to NT at baseline whereas this effect was further exaggerated after DOCA-salt (% relaxation at 10-5 M, S-P467L: 56.1±8.3, NT: 79.4±5.6, p<0.05 vs NT). Vascular morphology at luminal pressure of 75 mmHg showed a significant increase in wall thickness (S-P467L: 18.7±0.8, NT: 16.0±0.4, p<0.05 vs NT) and % media/lumen (S-P467L: 8.4±0.3, NT: 7.1±0.2, p<0.05 vs NT) in S-P467L MA after DOCA-salt. Expression of tissue inhibitor of metalloproteinases (TIMP)-4 and regulator of G-protein signaling (RGS)-5 transcript were 2- and 3.5-fold increased, respectively, in MA of NT with DOCA-salt compared to NT baseline. However, this induction was markedly blunted in S-P467L MA. We conclude that interference with PPARG function in SMC leads to altered gene expression crucial for normal vascular homeostasis, thereby sensitizing the mice to the effects of DOCA-salt induced HT and vascular dysfunction.

scholarly journals Baroreceptor denervation reduces inflammatory status but worsens cardiovascular collapse during systemic inflammation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mateus R. Amorim ◽  
Júnia L. de Deus ◽  
Camila A. Pereira ◽  
Luiz E. V. da Silva ◽  
Gabriela S. Borges ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Cardiovascular Collapse ◽  
Inflammatory Status

scholarly journals The Gut Microbiota Is Associated with Vascular Function and Blood Pressure Phenotypes in Overweight and Obese Middle-Aged/Older Adults (P21-024-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sarah Johnson ◽  
Nicole Litwin ◽  
Hannah Van Ark ◽  
Shannon Hartley ◽  
Emily Fischer ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arterial Stiffness ◽  
Gut Microbiota ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Reactive Hyperemia ◽  
Bifidobacterium Longum ◽  
Middle Aged ◽  
Principal Coordinates ◽  
The Relationship

Abstract Objectives The gut microbiota is emerging as an important regulator of cardiovascular health. Indeed, gut dysbiosis is increasingly being linked to the development of cardiovascular disease (CVD). Aging and obesity are associated with the development of CVD largely due to the development of vascular dysfunction, namely endothelial dysfunction and arterial stiffness. The objective of this study was to examine the relationship between the gut microbiota, blood pressure, and vascular function in aging overweight and obese individuals. Methods This cross-sectional study included fifteen overweight and obese (mean body mass index, BMI: 29.5; range: 25.8–37.0) middle-aged/older men and postmenopausal women (mean age: 53; range: 42–64 years). Blood pressure, arterial stiffness (augmentation index, AIx, and aortic pulse wave velocity, aPWV), and endothelial function (reactive hyperemia index, RHI) were assessed. Stool samples were collected for gut microbiota analysis using 16S ribosomal RNA sequencing. Principal coordinates analysis and Pearson's correlations were performed to evaluate the relationship between the gut microbiota and measures of vascular function and blood pressure. Results Global gut microbiota phenotypes clustered most strongly by aPWV (groups separated by median value) as visualized by Non-Metric Dimensional Scaling plot of Bray-Curtis Distances (stress = 0.09; P = 0.07). Several bacterial taxa correlated with vascular parameters. For example, Bifidobacterium longum (r = 0.80, P < 0.001) and Akkermansia muciniphila (r = 0.56, P = 0.047) were positively correlated with RHI. Bifdobacterium bifidum (r = −0.61, P = 0.02) and Oxalobacter formigenes (r = −0.62, P = 0.02) were negatively correlated with systolic blood pressure. Interestingly, there was no significant clustering by BMI groupings (overweight vs. obese) or correlations between BMI and specific taxa. Conclusions These preliminary data suggest that the gut microbiota is linked to vascular dysfunction and increased blood pressure in aging overweight and obese individuals independent of BMI. Further data collection and analysis are currently underway to explore these relationships in a larger human cohort, and to explore underlying mechanisms through transferring of vascular phenotypes in humans to germ-free mice through microbiota transplantation. Funding Sources NIFA, USDA.

scholarly journals Salt-Sensitivity of Blood Pressure and Insulin Resistance

2021 ◽  
Vol 12 ◽  
Author(s):  
Lale A. Ertuglu ◽  
Fernando Elijovich ◽  
Cheryl L. Laffer ◽  
Annet Kirabo
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Insulin Sensitivity ◽  
Immune Activation ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Salt Sensitivity ◽  
Common Denominator ◽  
Peroxisome Proliferator ◽  
Cardiovascular Morbidity And Mortality

Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular morbidity and mortality that is seen in both hypertensive and normotensive populations. Insulin resistance (IR) strongly correlates with SSBP and affects nearly 50% of salt sensitive people. While the precise mechanism by which IR and SSBP relate remains elusive, several common pathways are involved in the genesis of both processes, including vascular dysfunction and immune activation. Vascular dysfunction associated with insulin resistance is characterized by loss of nitric oxide (NO)-mediated vasodilation and heightened endothelin-1 induced vasoconstriction, as well as capillary rarefaction. It manifests with increased blood pressure (BP) in salt sensitive murine models. Another common denominator in the pathogenesis of insulin resistance, hypertension, and salt sensitivity (SS) is immune activation involving pro-inflammatory cytokines like tumor necrosis factor (TNF)-α, IL-1β, and IL-6. In the last decade, a new understanding of interstitial sodium storage in tissues such as skin and muscle has revolutionized traditional concepts of body sodium handling and pathogenesis of SS. We have shown that interstitial Na+ can trigger a T cell mediated inflammatory response through formation of isolevuglandin protein adducts in antigen presenting cells (APCs), and that this response is implicated in salt sensitive hypertension. The peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that modulates both insulin sensitivity and BP. PPARγ agonists increase insulin sensitivity and ameliorate salt sensitivity, whereas deficiency of PPARγ results in severe insulin resistance and hypertension. These findings suggest that PPARγ plays a role in the common pathogenesis of insulin sensitivity and salt sensitivity, perhaps via effects on the immune system and vascular function. The goal of this review is to discuss those mechanisms that may play a role in both SSBP and in insulin resistance.

scholarly journals Sexual dimorphism in the acute effects of secondhand smoke on thyroid hormone secretion, inflammatory markers and vascular function

2008 ◽  
Vol 294 (2) ◽  
pp. E456-E462 ◽  
Author(s):  
Andreas D. Flouris ◽  
Giorgos S. Metsios ◽  
Athanasios Z. Jamurtas ◽  
Yiannis Koutedakis
Keyword(s):  
Blood Pressure ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Systolic Blood Pressure ◽  
Inflammatory Cytokines ◽  
Secondhand Smoke ◽  
Vascular Function ◽  
Hormone Secretion ◽  
Gonadal Hormones ◽  
Free Thyroxine

Experimental evidence for the physiological effects of secondhand smoke (SHS) is limited, although it affects millions of people globally and its prevalence is increasing, despite currently adopted antismoking measures. Also, scarce evidence suggests that the effects of SHS may be more pronounced in men. We conducted a randomized single-blind crossover study to investigate the sex-specific SHS effects in a controlled simulated bar/restaurant environment on gonadal and thyroid hormones, inflammatory cytokines, and vascular function. Twenty-eight (women = 14) nonsmoking adults underwent a 1-h exposure to moderate SHS and a 1-h control trial. Serum and urine cotinine, gonadal and thyroid hormones, inflammatory cytokines, heart rate, and arterial blood pressure were assessed before exposure and immediately after in both trials. Results showed that testosterone ( P = 0.019) and progesterone ( P < 0.001) in men and 17β-estradiol ( P = 0.001) and progesterone ( P < 0.001) in women were significantly decreased after SHS. In men, SHS was accompanied by increased free thyroxine ( P < 0.001), triiodothyronine ( P = 0.020), and decreased the triiodothyronine-to-free thyroxine ratio ( P = 0.033). In women, significant SHS-induced change was observed only in free thyroxine ( P = 0.010), with considerable sex variation in free thyroxine and triiodothyronine and a decrease in luteinizing hormone ( P = 0.026) and follicle-stimulating hormone ( P < 0.001). After SHS, IL-1β ( P = 0.001) and systolic blood pressure ( P = 0.040) were increased in men but not women. We concluded that a 1-h SHS exposure at bar/restaurant levels is accompanied by decrements in gonadal hormones in both sexes and marked increases in thyroid hormone secretion, IL-1β production, and systolic blood pressure in men.

scholarly journals Plasma cytokine response during the postprandial period: a potential causal process in vascular disease?

2005 ◽  
Vol 93 (1) ◽  
pp. 3-9 ◽  
Author(s):  
Graham C. Burdge ◽  
Philip C. Calder
Keyword(s):  
Inflammatory Cytokines ◽  
Vascular Endothelium ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Causal Mechanism ◽  
Causal Process ◽  
Fatty Meal ◽  
Postprandial Lipaemia ◽  
Soluble Adhesion Molecules ◽  
Pro Inflammatory Cytokines

Chronic inflammation of the vascular endothelium produces endothelial dysfunction and ultimately atherogenesis. Postprandial hyperlipidaemia is an independent risk factor for cardiovascular disease. Recent studies show that the magnitude of postprandial lipaemia following a single fatty meal is negatively related to vascular function. This is associated with a transient increase in the concentrations of pro-inflammatory cytokines and soluble adhesion molecules and in pro-oxidant activity. One possible interpretation is that repeated exposure of the blood vessel wall to the activities of pro-inflammatory cytokines and pro-oxidants may damage the vascular endothelium and promote atherogenesis. Based on these results, we propose a model of a causal mechanism to explain how consumption of a fatty meal may impair vascular dysfunction.

scholarly journals 30 YEARS OF THE MINERALOCORTICOID RECEPTOR: The role of the mineralocorticoid receptor in the vasculature

2017 ◽  
Vol 234 (1) ◽  
pp. T67-T82 ◽  
Author(s):  
Jennifer J DuPont ◽  
Iris Z Jaffe
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Mineralocorticoid Receptor ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Vascular Inflammation ◽  
Kidney Injury ◽  
Vascular Pathology ◽  
The Impact

Since the mineralocorticoid receptor (MR) was cloned 30 years ago, it has become clear that MR is expressed in extra-renal tissues, including the cardiovascular system, where it is expressed in all cells of the vasculature. Understanding the role of MR in the vasculature has been of particular interest as clinical trials show that MR antagonism improves cardiovascular outcomes out of proportion to changes in blood pressure. The last 30 years of research have demonstrated that MR is a functional hormone-activated transcription factor in vascular smooth muscle cells and endothelial cells. This review summarizes advances in our understanding of the role of vascular MR in regulating blood pressure and vascular function, and its contribution to vascular disease. Specifically, vascular MR contributes directly to blood pressure control and to vascular dysfunction and remodeling in response to hypertension, obesity and vascular injury. The literature is summarized with respect to the role of vascular MR in conditions including: pulmonary hypertension; cerebral vascular remodeling and stroke; vascular inflammation, atherosclerosis and myocardial infarction; acute kidney injury; and vascular pathology in the eye. Considerations regarding the impact of age and sex on the function of vascular MR are also described. Further investigation of the precise molecular mechanisms by which MR contributes to these processes will aid in the identification of novel therapeutic targets to reduce cardiovascular disease (CVD)-related morbidity and mortality.

scholarly journals Vascular Alterations Among Young Adults with SARS-CoV-2

2020 ◽  
Author(s):  
Stephen M. Ratchford ◽  
Jonathon Lee Stickford ◽  
Valesha M Province ◽  
Nina Stute ◽  
Marc Andrew Augenreich ◽  
...  
Keyword(s):  
Young Adults ◽  
Arterial Stiffness ◽  
Systemic Inflammation ◽  
Vascular Function ◽  
Disease Risk ◽  
Vascular Dysfunction ◽  
Cardiovascular Disease Risk ◽  
Area Under The Curve ◽  
Control Group ◽  
Cross Sectional

Background: While SARS-CoV-2 primarily affects the lungs, the virus may be inflicting detriments to the cardiovascular system, both directly through angiotensin converting enzyme 2 receptor as well as initiating systemic inflammation. Persistent systemic inflammation may be provoking vascular dysfunction, an early indication of cardiovascular disease risk. Methods: In order to establish the potential effects of SARS-CoV-2 on the systemic vasculature in the arms and legs, we performed a cross-sectional analysis of young healthy adults (Control: 5M/15F, 23.0±1.3y, 167±9cm, 63.0±7.4kg) and young adults who, 3-4 weeks prior to testing, had tested positive for SARS-CoV-2 (SARS-CoV-2: 4M/7F, 20.2±1.1y, 172±12cm, 69.5±12.4kg) (mean±SD). Using Doppler ultrasound, brachial artery flow-mediated dilation (FMD) in the arm and single passive limb movement (sPLM) in the leg were assessed as markers of vascular function. Pulse wave velocity (PWVcf) was assessed as a marker of arterial stiffness. Results: FMD was lower in the SARS-CoV-2 group (2.71±1.21%) compared to the Control group (8.81±2.96%) (P<0.01) and when made relative to the shear stimulus (SARS-CoV-2: 0.04±0.02AU, Control: 0.13±0.06AU, P<0.01). The femoral artery blood flow response, as evidenced by the area under the curve, from the sPLM was lower in the SARS-CoV-2 group (-3±91ml) compared with the Control group (118±114ml) (P<0.01). PWVcf was higher in the SARS-CoV-2 group (5.83±0.62m/s) compared with the Control group (5.17±0.66m/s) (P<0.01). Conclusions: Significantly lower systemic vascular function and higher arterial stiffness are evident weeks after testing positive for SARS-CoV-2 among young adults compared to controls.

Abstract 057: Nox5 Induces Vascular Dysfunction and Arterial Remodelling Independently of Blood Pressure Elevation in Ang II-infused Nox5-expressing Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Augusto C Montezano ◽  
Adam P Harvey ◽  
Francisco J Rios ◽  
Maria Dulak-Lis ◽  
Wendy Beatie ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Kinase Inhibitor ◽  
Vascular Dysfunction ◽  
Rho Kinase ◽  
Lumen Diameter ◽  
Ang Ii ◽  
Cross Sectional ◽  
Blood Pressure Elevation ◽  
Endothelium Dependent Relaxation

Nox5 is a unique Ca 2+ -sensitive Nox isoform that is expressed in human vascular smooth muscle cells (VSMC). Although Nox5 has been implicated in diabetic nephropathy, its role in vascular function and development of hypertension remain unclear. Nox5 is not expressed in rodents, and accordingly we generated humanised Nox5 mice with Nox5 expressed in a VSMC-specific manner (Nox5SM22). Control (wild-type) and Nox5SM22 mice were infused with Ang II (600 ng/Kg/day). Blood pressure (BP) was assessed by tail-cuff. Vascular function and structure of resistance arteries were measured by myography. Ang II increased BP in WT (182.5±10 mmHg) and Nox5SM22 mice (173.1±5 mmHg) with no significant differences. Arteries from Nox5SM22 mice exhibited reduced endothelium-dependent relaxation versus WT controls (%ACh relaxation: 55.1±4 vs ctl: 81.6±7%). Fasudil (Rho kinase inhibitor)-induced relaxation was reduced in Nox5SM22 mice versus controls (%Fas: 111.3±11 vs ctl: 166.6±8%) (p<0.05). Ang II increased the maximal contraction to U46619 (thromboxane A2 mimetic) in WT (115.8±2 vs untreated: 101.4±2%) and Nox5SM22 (121.3±3 vs untreated: 99.1±2) (p<0.05) and induced endothelial dysfunction in all groups. Fasudil-induced relaxation was impaired by Ang II in WT (102.7±6 vs untreated: 166.6±8%, p<0.05) but not further impaired in Nox5SM22 mice (114.9±6 vs untreated: 111.3±11%). Ang II increased cross-sectional area (CSA) and lumen diameter; while in Nox5SM22 mice, Ang II increased wall thickness, wall-to-lumen ratio, CSA and decreased lumen diameter, with associated increased vascular stiffness. Our findings indicate that in mice expressing human Nox5 in VSMCs, endothelium-dependent relaxation is impaired, fasudil-mediated vasodilation is attenuated and vessels undergo exaggerated hypertrophic inward remodelling with increased stiffness; processes that occur independently of BP elevation. These data suggest an important role for Nox5 in Ang II-induced vascular dysfunction and remodeling, but not in the development of hypertension. Moreover, we identify Rho kinase as a putative target for Nox5-induced vascular injury. We provide novel insights into Nox5 vascular biology and demonstrate that vascular Nox5 actions are dissociated from BP effects.

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