Selective PDE1 inhibition ameliorates vascular function, reduces inflammatory response, and lowers blood pressure in ageing animals

2021 ◽  
pp. JPET-AR-2021-000628
Author(s):  
Keivan Golshiri ◽  
Ehsan Ataei Ataabadi ◽  
Eloísa Rubio-Beltran ◽  
Sophie Dutheil ◽  
Wei Yao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Inflammatory Response ◽  
Vascular Function

Atopic dermatitis: new horizons of therapy

2019 ◽  
Vol 1 (7) ◽  
pp. 29-32 ◽  
Author(s):  
L. S. Kruglova ◽  
E. M. Gensler
Keyword(s):  
Blood Pressure ◽  
Immune Response ◽  
Allergic Rhinitis ◽  
Atopic Dermatitis ◽  
Targeted Therapy ◽  
Inflammatory Response ◽  
Bronchial Asthma ◽  
New Horizons ◽  
The Past

Over the past decades, the first breakthrough milestone in the treatment of severe forms of atopic dermatitis (AD) has been targeted therapy aimed at inhibiting IL-4 and IL-13. This was made possible thanks to advances in the understanding of the pathogenesis of AD, the driver of which is the Th2-type immune response, which also underlies such manifestations of atopy as bronchial asthma, allergic rhinitis, and polynosis. In the case of the Th2-type immune response, cytokines IL-4 and IL-13 are secreted, which are the main promoters of the inflammatory response in AD. Inhibition of IL-4 and IL-13 leads to the prevention of inflammation and is an effective approach to therapy. The use of therapy aimed at inhibition of cytokines allows you to effectively cope with the manifestations of severe and moderately severe blood pressure.

Cardiovascular Responses to Muscle Stretching: A Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Ewan Thomas ◽  
Marianna Bellafiore ◽  
Ambra Gentile ◽  
Antonio Paoli ◽  
Antonio Palma ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiovascular System ◽  
Vascular Function ◽  
Meta Analysis ◽  
Random Effect ◽  
Cardiovascular Responses ◽  
Qualitative Description ◽  
Cross Sectional ◽  
Quantitative Synthesis

AbstractThe aim of this study will be to review the current body of literature to understand the effects of stretching on the responses of the cardiovascular system. A literature search was performed using the following databases: Scopus, NLM Pubmed and ScienceDirect. Studies regarding the effects of stretching on responses of the cardiovascular system were investigated. Outcomes regarded heart rate(HR), blood pressure, pulse wave velocity (PWV of which baPWV for brachial-ankle and cfPWV for carotid-femoral waveforms), heart rate variability and endothelial vascular function. Subsequently, the effects of each outcome were quantitatively synthetized using meta-analytic synthesis with random-effect models. A total of 16 studies were considered eligible and included in the quantitative synthesis. Groups were also stratified according to cross-sectional or longitudinal stretching interventions. Quality assessment through the NHLBI tools observed a “fair-to-good” quality of the studies. The meta-analytic synthesis showed a significant effect of d=0.38 concerning HR, d=2.04 regarding baPWV and d=0.46 for cfPWV. Stretching significantly reduces arterial stiffness and HR. The qualitative description of the studies was also supported by the meta-analytic synthesis. No adverse effects were reported, after stretching, in patients affected by cardiovascular disease on blood pressure. There is a lack of studies regarding vascular adaptations to stretching.

scholarly journals Biomarker-estimated flavan-3-ol intake is associated with lower blood pressure in cross-sectional analysis in EPIC Norfolk

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Javier I. Ottaviani ◽  
Abigail Britten ◽  
Debora Lucarelli ◽  
Robert Luben ◽  
Angela A. Mulligan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Vascular Function ◽  
Cardiovascular Health ◽  
Vascular Diseases ◽  
Inverse Association ◽  
Cvd Risk ◽  
Lower Systolic Blood Pressure ◽  
Cross Sectional ◽  
Salt Reduction

Abstract Flavan-3-ols are a group of bioactive compounds that have been shown to improve vascular function in intervention studies. They are therefore of great interest for the development of dietary recommendation for the prevention of cardio-vascular diseases. However, there are currently no reliable data from observational studies, as the high variability in the flavan-3-ol content of food makes it difficult to estimate actual intake without nutritional biomarkers. In this study, we investigated cross-sectional associations between biomarker-estimated flavan-3-ol intake and blood pressure and other CVD risk markers, as well as longitudinal associations with CVD risk in 25,618 participants of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort. High flavan-3-ol intake, achievable as part of an habitual diet, was associated with a significantly lower systolic blood pressure (− 1.9 (− 2.7; − 1.1) mmHg in men and − 2.5 (− 3.3; − 1.8) mmHg in women; lowest vs highest decile of biomarker), comparable to adherence to a Mediterranean Diet or moderate salt reduction. Subgroup analyses showed that hypertensive participants had stronger inverse association between flavan-3-ol biomarker and systolic blood pressure when compared to normotensive participants. Flavanol intake could therefore have a role in the maintenance of cardiovascular health on a population scale.

scholarly journals Vascular-ventricular coupling during exercise is not affected by exaggerated blood pressures in endurance-trained athletes

2019 ◽  
Vol 127 (3) ◽  
pp. 753-759 ◽  
Author(s):  
Katharine D. Currie ◽  
Zion Sasson ◽  
Jack M. Goodman
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Arterial Compliance ◽  
Left Ventricular ◽  
Left Ventricular Volumes ◽  
Peripheral Vascular ◽  
Arterial Elastance ◽  
Coupling Index ◽  
Cardiovascular Performance ◽  
Stage 1

This study sought to examine whether cardiovascular performance during exercise, assessed using the vascular-ventricular coupling index (VVC), was affected by exaggerated blood pressure (EBP) responses in endurance-trained athletes. Subjects were middle-aged endurance-trained men and women. Blood pressure measurements and left ventricular echocardiography were performed in a semiupright position at rest and during steady-state cycling at workloads that elicited 100–110 beats/min ( stage 1) and 130–140 beats/min ( stage 2). These data were used to calculate effective arterial elastance index ( EaI), left ventricular end-systolic elastance index ( ELVI), and their ratio (VVC). Additional measurements of left ventricular volumes and function (i.e., stroke volume, cardiac output, and longitudinal strain) and indirect assessments of peripheral vascular function (i.e., total arterial compliance and peripheral vascular resistance) were examined. Fourteen subjects with EBP (EBP+, 50% men) and 14 sex-matched subjects without EBP (EBP−) participated, with results presented as EBP+ versus EBP−. EaI and ELVI increased from rest to exercise while VVC decreased, but only ELVI was different between groups at stage 1 [7.6 (1.8) vs. 6.4 (1.0) mmHg·ml−1·m−2, P = 0.045] and stage 2 [10.3 (1.6) vs. 8.0 (1.7) mmHg·ml−1·m−2, P < 0.001]. Additional comparisons revealed no group difference in the contribution of the Frank-Starling mechanism or left ventricular and peripheral vascular function during exercise. The cardiovascular adjustment to exercise in athletes with EBP is achieved through a matched increase in both EaI and ELVI, and the absence of between-group differences in left ventricular or peripheral vascular function suggests that other factors may contribute to the EBP response. NEW & NOTEWORTHY Cardiovascular performance during submaximal exercise, assessed using vascular-ventricular coupling, is unaffected by exaggerated blood pressure (EBP) responses in endurance-trained athletes. The underlying mechanisms of EBP in athletes remain unknown as changes in left ventricular and peripheral vascular function during exercise were similar in athletes with and without EBP.

Reno-protective mechanisms of epoxyeicosatrienoic acids in cardiovascular disease

2012 ◽  
Vol 302 (3) ◽  
pp. R321-R330 ◽  
Author(s):  
Ahmed A. Elmarakby
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Animal Models ◽  
Vascular Function ◽  
Organ Damage ◽  
Reduce Blood Pressure ◽  
Experimental Models ◽  
Epoxyeicosatrienoic Acids ◽  
Protective Effects ◽  
Protective Mechanisms

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and it is well known that end-stage renal disease (ESRD) is a profound consequence of the progression of CVD. Present treatments only slow CVD progression to ESRD, and it is imperative that new therapeutic strategies are developed to prevent the incidence of ESRD. Because epoxyeicosatrienoic acids (EETs) have been shown to elicit reno-protective effects in hypertensive animal models, the current review will focus on addressing the reno-protective mechanisms of EETs in CVD. The cytochrome P-450 epoxygenase catalyzes the oxidation of arachidonic acid to EETs. EETs have been identified as endothelium-derived hyperpolarizing factors (EDHFs) with vasodilatory, anti-inflammatory, antihypertensive, and antiplatelet aggregation properties. EETs also have profound effects on vascular migration and proliferation and promote angiogenesis. The progression of CVD has been linked to decreased EETs levels, leading to the concept that EETs should be therapeutically targeted to prevent end-organ damage associated with CVD. However, EETs are quickly degraded by the enzyme soluble epoxide hydrolase (sEH) to their less active diols, dihydroxyeicosatrienoic acids (DHETs). As such, one way to increase EETs level is to inhibit their degradation to DHETs by using sEH inhibitors. Inhibition of sEH has been shown to effectively reduce blood pressure and organ damage in experimental models of CVD. Another approach to target EETs is to develop EET analogs with improved solubility and resistance to auto-oxidation and metabolism by sEH. For example, stable ether EET analogs dilate afferent arterioles and lower blood pressure in hypertensive rodent animal models. EET agonists also improve insulin signaling and vascular function in animal models of metabolic syndrome.

scholarly journals Effects of Cranberry Juice Supplementation on Cardiovascular Disease Risk Factors in Adults with Elevated Blood Pressure: A Randomized Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2618
Author(s):  
Chesney K. Richter ◽  
Ann C. Skulas-Ray ◽  
Trent L. Gaugler ◽  
Stacey Meily ◽  
Kristina S. Petersen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Systolic Blood Pressure ◽  
Vascular Function ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Lipoprotein Profile ◽  
Cranberry Juice ◽  
Central Systolic Blood Pressure

Emerging cardiovascular disease (CVD) risk factors, including central vascular function and HDL efflux, may be modifiable with food-based interventions such as cranberry juice. A randomized, placebo-controlled, crossover trial was conducted in middle-aged adults with overweight/obesity (n = 40; mean BMI: 28.7 ± 0.8 kg/m2; mean age: 47 ± 2 years) and elevated brachial blood pressure (mean systolic/diastolic BP: 124 ± 2/81 ± 1 mm Hg). Study participants consumed 500 mL/d of cranberry juice (~16 fl oz; 27% cranberry juice) or a matched placebo juice in a randomized order (8-week supplementation periods; 8-week compliance break), with blood samples and vascular measurements obtained at study entry and following each supplementation period. There was no significant treatment effect of cranberry juice supplementation on the primary endpoint of central systolic blood pressure or central or brachial diastolic pressure. Cranberry juice significantly reduced 24-h diastolic ambulatory BP by ~2 mm Hg compared to the placebo (p = 0.05) during daytime hours. Cranberry juice supplementation did not alter LDL-C but significantly changed the composition of the lipoprotein profile compared to the placebo, increasing the concentration of large LDL-C particles (+29.5 vs. −6.7 nmol/L; p = 0.02) and LDL size (+0.073 vs. −0.068 nm; p = 0.001). There was no effect of treatment on ex vivo HDL efflux in the total population, but exploratory subgroup analyses identified an interaction between BMI and global HDL efflux (p = 0.02), with greater effect of cranberry juice in participants who were overweight. Exploratory analyses indicate that baseline C-reactive protein (CRP) values may moderate treatment effects. In this population of adults with elevated blood pressure, cranberry juice supplementation had no significant effect on central systolic blood pressure but did have modest effects on 24-hr diastolic ambulatory BP and the lipoprotein profile. Future studies are needed to verify these findings and the results of our exploratory analyses related to baseline health moderators.

Higher systolic blood pressure with normal vascular function measurements in preterm-born children

2014 ◽  
Vol 103 (9) ◽  
pp. 904-912 ◽  
Author(s):  
Martin O. Edwards ◽  
William John Watkins ◽  
Sarah J. Kotecha ◽  
Julian P. J. Halcox ◽  
Frank D. Dunstan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Vascular Function ◽  
Preterm Born

scholarly journals Activation of angiotensin type 2 receptor attenuates testosterone-induced hypertension and uterine vascular resistance in pregnant rats

2021 ◽  
Author(s):  
Jay S Mishra ◽  
Sathish Kumar
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Vascular Function ◽  
Uterine Artery ◽  
Artery Blood Flow ◽  
Protein Levels ◽  
Angiotensin Type 2 Receptor ◽  
Enos Protein ◽  
Angiotensin Type

Abstract Preeclampsia is a pregnancy-related hypertensive disorder with unclear mechanisms. While hypersensitivity to angiotensin II via vasoconstrictive angiotensin type-1 receptor (AT1R) is observed in preeclampsia, the importance of vasodilatory angiotensin type-2 receptor (AT2R) in the control of vascular dysfunction is less clear. We assessed whether AT1R, AT2R and eNOS expression is altered in placental vessels of preeclamptic women and tested if ex vivo incubation with AT2R agonist Compound 21 (C21; 1 μM) could restore AT1R, AT2R and eNOS balance. Further, using a rat model of gestational hypertension induced by elevated testosterone, we examined whether C21 (1 μg·kg−1·day−1, oral) could preserve AT1R and AT2R balance and improve blood pressure, uterine artery blood flow, and vascular function. Western blots revealed that AT1R protein level was higher while AT2R and eNOS protein were reduced in preeclamptic placental vessels, and AT2R agonist C21 decreased AT1R and increased AT2R and eNOS protein levels in preeclamptic vessels. In testosterone-dams, blood pressure was higher, and uterine artery blood flow was reduced, and C21 treatment reversed these levels similar to those in controls dams. C21 attenuated the exaggerated Ang II contraction and improved endothelium-dependent vasorelaxation in uterine arteries of testosterone-dams. These C21-mediated vascular effects were associated with decreased AT1R and increased AT2R and eNOS protein levels. C21 also increased serum nitrate/nitrite and bradykinin production in testosterone-dams and attenuated the feto-placental growth restriction. Thus, AT1R upregulation and AT2R downregulation is observed in preeclampsia and testosterone-model, and increasing AT2R activity could help restore AT1R and AT2R balance and improve gestational vascular function.

Abstract 13170: Endothelial Function is Impaired in Relation to Alcohol Consumption in Men in a Large General Population

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Nozomu Oda ◽  
Yukihito Higashi ◽  
Masato Kajikawa ◽  
Tatsuya Maruhashi ◽  
Akimichi Iwamoto ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Alcohol Consumption ◽  
General Population ◽  
Endothelial Function ◽  
Vascular Function ◽  
Density Lipoprotein ◽  
Self Report ◽  
Lipoprotein Cholesterol ◽  
Adjusted Risk ◽  
Significant Difference

Introduction: Endothelial function is impaired in heavy or binge drinking. Heavy drinking should be a predictor of endothelial dysfunction. However, there is little information on the effects of dose-dependent alcohol consumption on endothelial function. Therefore, we evaluated the relationship between alcohol consumption and endothelial function in a large general population. Methods and Results: We measured flow-mediated vasodilation (FMD) in 2734 men who provided self-report about habitual alcohol intake. The subjects were divided into five groups by alcohol consumption: none (0 g/week), light (0 g/week< to ≤140 g/week), moderate (140 g/week< to ≤280 g/week), heavy (280 g/week< to ≤420 g/week), and excessive (420 g/week<). Age, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, gamma glutamyl transpeptidase, uric acid, plasma glucose, hemoglobin A1c, and current smoking were significantly correlated with alcohol consumption. FMD showed a gradual decrease according to increased alcohol consumption (none, 6.6±3.4%; light, 6.2±3.0%; moderate, 6.0±3.0%; heavy, 5.5±2.9%; excessive, 5.3±3.0%; P<0.01). There was a significant difference in FMD between the non-drinker group and the light drinker group (P=0.018). After adjusted risk factors, we showed the significantly smaller FMD in the 4 drinker groups than in the non-drinker group: light drinker group (OR, 1.38; 95% CI, 1.10 to 1.75), moderate drinker group (OR, 1.36; 95% CI, 1.01 to 1.82), heavy drinker group (OR, 2.05; 95% CI, 1.46 to 2.87), excessive drinker group (OR, 2.04; 95% CI, 1.43 to 2.89). Conclusions: These findings suggest that even light alcohol consumption impair the endothelial function. Alcohol drinking may be harmful for vascular function.

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