Abstract P124: Blood Pressure Characterization In Btg2 Mutant Rat

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Matthew Hoffman ◽  
Akiko Takizawa ◽  
Eric Jensen ◽  
Rebecca Schilling ◽  
Michael Grzybowski ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Signaling Pathways ◽  
Complex Disease ◽  
Cell Cycle Gene ◽  
Dietary Salt ◽  
Genetic Determinants ◽  
Therapeutic Approaches ◽  
Skeletal Morphology ◽  
Environmental Interactions ◽  
Modifiable Factors

Hypertension (HTN) is a complex disease influenced by heritable genetic elements and environmental interactions. Dietary salt is among the most influential modifiable factors contributing to increased blood pressure (BP). It is well established that men and women develop BP impairment in different patterns and a recent emphasis has been placed on identifying mechanisms leading to the differences observed between the sexes in HTN development. The current work reported here builds on an extensive genetic mapping experiment which sought to identify genetic determinants of salt sensitive (SS) HTN using the Dahl SS rat. BTG anti-proliferation factor 2 ( Btg2 ) was previously isolated by our group using congenic breeding experiments which identified it as a female causative SS HTN candidate gene. In the current study, Btg2 was mutated using TALEN targeted gene disruption on the SSBN congenic rat background. The Btg2 mutated rats exhibited impaired BP and proteinuria responses to a high salt diet compared to wild type littermates. Differences in body weight, mutant pup viability, skeletal morphology, and adult nephron density suggest a potential role for Btg2 in developmental signaling pathways. Subsequent cell cycle gene expression assessment provides several additional signaling pathways that Btg2 may function through during salt handling in the kidney. The expression analysis also indicates several upstream targets that can be explored to further isolate therapeutic approaches for SS HTN.

Excessive salt intake is a significant predictor for future development of metabolic syndrome in the general population

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Takase ◽  
M Machii ◽  
D Nonaka ◽  
K Ohno ◽  
S Takayama ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Cardiovascular Diseases ◽  
General Population ◽  
Future Development ◽  
Salt Intake ◽  
Smoking Habit ◽  
Dietary Salt ◽  
Modifiable Factors ◽  
Female Subjects

Abstract Background/Introduction Dietary salt consumption is one of the most important modifiable factors in our lifestyle and restriction of dietary salt results in the reduction of blood pressure in previous studies. Excessive salt intake causes cardiovascular diseases independently of its effects on blood pressure. Since metabolic syndrome also increases a risk of cardiovascular disease, there may be some association between salt intake and metabolic syndrome. Purpose The present study was designed to investigate a possible relationship between salt intake and future development of metabolic syndrome in the general population. Methods Consecutive 12,256 subjects without metabolic syndrome (male=7,053, 52.1±12.3 year-old) who visited our hospital for an annual physical check-up from April 2010 to March 2018 were enrolled. After baseline examination, subjects were followed up until March 2019 (median 1,582 days) with the endpoint being the development of metabolic syndrome. Metabolic syndrome was diagnosed according to the Japanese criteria (2005). Individual salt intake was estimated using a spot urine by a previously reported method. Results Salt intake was 11.9±3.0 g/day in male and 8.2±2.1 g/day in female subjects at baseline. During the follow-up period, 1,669 subjects developed metabolic syndrome (29.9 per 1,000 person-year) with the incidence being more frequent in male than female subjects (41.8 vs. 14.2 per 1,000 person-year). Non-adjusted hazard ratio (HR) (95% confidence interval [CI]) of salt intake for the development of metabolic syndrome was 1.157 (1.142–1.173). In analysis where subjects were divided into gender-specific quartiles according to the baseline salt intake, Kaplan-Meyer curve analysis revealed that the incidence of metabolic syndrome were increased across the quartiles (20.6, 25.0, 32.4, and 42.7 per 1,000 person-years; logrank p<0.001). Multivariate Cox proportional hazard analysis adjusted for age, gender, body mass index, systolic blood pressure, heart rate, serum creatinine, uric acid, fasting plasma glucose, low-density lipoprotein cholesterol, triglyceride, hemoglobin and current smoking habit at baseline revealed that salt intake predicted the new onset of metabolic syndrome (HR: 1.036, 95% CI: 1.019–1.054). Conclusions Excessive salt intake is significantly associated with the new development of metabolic syndrome in the general population. The results suggest that salt restriction prevents metabolic syndrome as well as hypertension leading to cardiovascular diseases. Funding Acknowledgement Type of funding source: None

Association of interactions between dietary salt consumption and hypertension-susceptibility genetic polymorphisms with blood pressure among Japanese male workers

2016 ◽  
Vol 21 (3) ◽  
pp. 457-464 ◽  
Author(s):  
Takahiro Imaizumi ◽  
Masahiko Ando ◽  
Masahiro Nakatochi ◽  
Shoichi Maruyama ◽  
Yoshinari Yasuda ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Genetic Polymorphisms ◽  
Dietary Salt ◽  
Salt Consumption ◽  
Japanese Male ◽  
Male Workers

scholarly journals Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jaakko Laaksonen ◽  
Pashupati P. Mishra ◽  
Ilkka Seppälä ◽  
Leo-Pekka Lyytikäinen ◽  
Emma Raitoharju ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mitochondrial Dna ◽  
Genome Wide Association Study ◽  
Rare Variants ◽  
Meta Analysis ◽  
Noncommunicable Diseases ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Genome Wide ◽  
Mitochondrial Dna Variants

AbstractHigh blood pressure (BP) is a major risk factor for many noncommunicable diseases. The effect of mitochondrial DNA single-nucleotide polymorphisms (mtSNPs) on BP is less known than that of nuclear SNPs. We investigated the mitochondrial genetic determinants of systolic, diastolic, and mean arterial BP. MtSNPs were determined from peripheral blood by sequencing or with genome-wide association study SNP arrays in two independent Finnish cohorts, the Young Finns Study and the Finnish Cardiovascular Study, respectively. In total, over 4200 individuals were included. The effects of individual common mtSNPs, with an additional focus on sex-specificity, and aggregates of rare mtSNPs grouped by mitochondrial genes were evaluated by meta-analysis of linear regression and a sequence kernel association test, respectively. We accounted for the predicted pathogenicity of the rare variants within protein-encoding and the tRNA regions. In the meta-analysis of 87 common mtSNPs, we did not observe significant associations with any of the BP traits. Sex-specific and rare-variant analyses did not pinpoint any significant associations either. Our results are in agreement with several previous studies suggesting that mtDNA variation does not have a significant role in the regulation of BP. Future studies might need to reconsider the mechanisms thought to link mtDNA with hypertension.

Potential therapeutic approaches in paraquat poisoning: a narrative review

2021 ◽  
Author(s):  
Amir Ghabousian ◽  
Saeed Safari ◽  
Niloufar Ansari
Keyword(s):  
Signaling Pathways ◽  
Cell Injury ◽  
Clinical Course ◽  
Medical Condition ◽  
Case Fatality ◽  
Therapeutic Approaches ◽  
Traditional Treatment ◽  
Current Review ◽  
Novel Therapeutic Strategies ◽  
Cell Signaling Pathways

Paraquat dichloride (PQ) poisoning is a relatively rare yet critical medical condition that has a high case fatality rate. Lung tissue is highly susceptible to PQ-induced injury, and respiratory failure is the leading cause of death in these patients. Unfortunately, there is a lack of an effective therapeutic approach to ameliorate outcomes. It is well-known that PQ interferes with a variety of cell signaling pathways and induces the generation of reactive oxygen species (ROS), which ultimately results in cell injury. The traditional treatment decisions have not been able to significantly change the clinical course of PQ poisoning. Moreover, novel therapeutic strategies for PQ poisoning have centered on the inhibition of PQ-induced signaling pathways. In the current review, we sought to provide a bird’s-eye view of the available therapeutic approaches in patients with PQ poisoning.

Abstract 16443: Effects of Dietary Salt Intakes on Blood Pressure, Renal Function and Oxidative Stress in Rats Treated With Candesartan

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Gangyi Zhu ◽  
Yanting Yu ◽  
Xiaoyan Wang
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Renal Function ◽  
Kidney Diseases ◽  
Sprague Dawley ◽  
Dietary Salt ◽  
Salt Restriction ◽  
Low Salt ◽  
Receptor Blockers ◽  
And Oxidative Stress

Candesartan is one of angiotensin II type1 receptor blockers(ARB) and commonly used as first-line antihypertensive treatment. Low salt diet is often recommended by clinicians to the patients with hypertension and kidney diseases. However,it is not clear whether salt restriction is beneficial to the patients taking ARB. In order to explore this problem, the impacts of different salt diets on blood pressure (BP),renal function and oxidative stress were determined in 2-3 months old male Sprague Dawley rats treated with candesartan. The rats were randomly divided into 4 groups fed agar-gelled food rationally with NaCl content at 0.01%, 0.8%, 2% and 4% respectively(4-7 rats/group) while all rats were intraperitoneally injected with candesartan at 1mg / kg / day for 7 days. SBP started to decline on day 2 in all except 4% NaCl groups relative to day 0 (recorded 5-6 hrs before the first injection). On day 6, systolic BP (mmHg, tail-cuff, Softron,BP-98A) was lower in 0.8% (103.7+2.3) & 0.01% (101.6+3) groups than 2% (113.5+4.1) & 4% (129.9+4.6) groups (one way ANOVA,LSD test, P<0.05) and correlated positively with food NaCl intakes (R 2 =0.9832). DBP was changed in a similar pattern as SBP. Serum creatinine (μmol/L) was higher in 0.01% group (225+39) than groups of 0.8% (1328+350), 2% (2095+242) and 4% (1576+703) while creatinine clearance (ml/day) was lower in 0.01% group (69.3+9) than groups of 0.8% (43.7+9), 2%(27.7+2) and 4%(29+0.6). In order to determine whether oxidative stress plays any role in the BP regulation and renal function maintenance, we also checked renal protein expression of ROS components. Relative to 0.8% group, renal NOXs were not altered in 0.01% group while NOX1 (145+18,% of 0.8% group), NOX2 (240+54) and NOX4 (197+41) was higher in 2% group than other groups. Mn-SOD (77+7.8), not Cu-Zn SOD, was decreased while HO1 (170+16), not HO2, was increased in 0.01% group. Renal abundance of nitrotyrosine was lower in 0.01% than other groups indicating a decreased oxidative stress, possibly caused by increase in HO1. We concluded that salt restriction with candesartan is beneficial to antihypertensive effect of AT1R blockade but disadvantage to maintenance of renal function. Thus, cautions to choice of low salt intakes are necessary when taking ARB agents.

Abstract P256: Genetic Determinants Of Blood Pressure Associate With Apparent Treatment Resistant Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Joseph H Breeyear ◽  
Megan M Shuey ◽  
Todd L Edwards ◽  
Jacklyn Hellwege
Keyword(s):  
Blood Pressure ◽  
Risk Scores ◽  
Uncontrolled Hypertension ◽  
Polygenic Risk Score ◽  
Genetic Determinants ◽  
Treatment Resistant ◽  
Polygenic Risk ◽  
Blood Pressures ◽  
The Uk ◽  
Hispanic White

Hypertension is estimated to affect more than 49.6% of US adults 20 years and older. Of those individuals with hypertension, more than ten million are classified as apparent treatment resistant hypertensive (aTRH). The attributable risk of uncontrolled hypertension was estimated to be 49% for cardiovascular disease and 62% for stroke. We developed a polygenic risk score (PRS) for systolic (SBP) and diastolic (DBP) blood pressure to examine the association between the genetic determinants of blood pressure and aTRH with the goal of identifying high risk individuals. The meta-analyzed transethnic results of Giri et al., Biobank Japan, and Liang et al. were used to generate a PRS with PRS-CS followed by p -value thresholding, and validation in the UK Biobank (n max =341,930). Associations were modeled with logistic regression adjusted for age, age-squared, BMI, sex, and ten principal components of ancestry in BioVU’s transethnic population (n max =37,978), as well as non-Hispanic Black (n max =5,026) and non-Hispanic White (n max =28,545) subsets. The SBP PRS was significantly associated with an increased aTRH risk in the non-Hispanic White subset (1.08 (1.04 - 1.12), p = 0.00037) and transethnic (1.08 (1.04 - 1.13), p = 0.00020) populations, but not the non-Hispanic Black subset. The DBP PRS was not associated with aTRH in any population. Our findings present evidence that individuals with a higher genetic predisposition towards hypertension are at higher risk of aTRH. By integrating polygenic risk scores and clinical covariates in prediction of aTRH, individuals’ therapeutic regimens may be tailored to help maintain stable blood pressures, therefore reducing their risk of comorbidities.

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