Polymorphisms of EDNRB, ATG, and ACE genes in salt-sensitive hypertensionThis article is one of a selection of papers published in the special issue (part 2 of 2) on Forefronts in Endothelin.

2008 ◽  
Vol 86 (8) ◽  
pp. 505-510 ◽  
Author(s):  
Jessica Caprioli ◽  
Caterina Mele ◽  
Chiara Mossali ◽  
Laura Gallizioli ◽  
Gilberta Giacchetti ◽  
...  
Keyword(s):  
Protective Role ◽  
Receptor Subtype ◽  
Genotype Distribution ◽  
High Salt Diet ◽  
Subtype B ◽  
Salt Depletion ◽  
Sensitivity Data ◽  
Pressure Changes ◽  
Salt Sensitive Hypertension

Almost 50% of hypertensive individuals manifest blood pressure changes in response to salt depletion or repletion and are termed “salt sensitive” (SS). Blunted activity of the endothelin (ET) system and the renin–angiotensin–aldosterone system (RAAS) have been reported as possible mechanisms contributing to salt sensitivity. Data are available that endothelin receptor subtype B (ETBR)-deficient rats develop salt-sensitive hypertension when fed a high-salt diet. Whether the ETBR gene (EDNRB) is involved in genetic predisposition to human salt-sensitive hypertension has not been studied so far. We screened EDNRB in 104 hypertensive patients (49 salt sensitive and 55 salt resistant) and 110 normotensive controls. No new sequence variation was found, but genotype distribution of the common polymorphism G1065A revealed that the AA + GA genotypes were significantly more frequent in salt-resistant than in salt-sensitive individuals (p = 0.007), suggesting a protective role for the A allele. We also screened angiotensinogen gene AGT M235T and angiotensin-converting enzyme insertion/deletion polymorphism ACE I/D and found an association between TT genotype and hypertension. A possible synergistic effect to salt-sensitive hypertension was found by combining EDNRB GG with ACE DD/ID genotypes. In conclusion, our data confirm the role of ET system and RAAS in salt-sensitive hypertension.

scholarly journals Metabolic Syndrome and Salt-Sensitive Hypertension in Polygenic Obese TALLYHO/JngJ Mice: Role of Na/K-ATPase Signaling

2019 ◽  
Vol 20 (14) ◽  
pp. 3495 ◽  
Author(s):  
Yanling Yan ◽  
Jiayan Wang ◽  
Muhammad A. Chaudhry ◽  
Ying Nie ◽  
Shuyan Sun ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Significant Rise ◽  
Protein Carbonylation ◽  
High Salt ◽  
Kidney Cortex ◽  
High Salt Diet ◽  
Salt Diet ◽  
Salt Sensitive Hypertension

We have demonstrated that Na/K-ATPase acts as a receptor for reactive oxygen species (ROS), regulating renal Na+ handling and blood pressure. TALLYHO/JngJ (TH) mice are believed to mimic the state of obesity in humans with a polygenic background of type 2 diabetes. This present work is to investigate the role of Na/K-ATPase signaling in TH mice, focusing on susceptibility to hypertension due to chronic excess salt ingestion. Age-matched male TH and the control C57BL/6J (B6) mice were fed either normal diet or high salt diet (HS: 2, 4, and 8% NaCl) to construct the renal function curve. Na/K-ATPase signaling including c-Src and ERK1/2 phosphorylation, as well as protein carbonylation (a commonly used marker for enhanced ROS production), were assessed in the kidney cortex tissues by Western blot. Urinary and plasma Na+ levels were measured by flame photometry. When compared to B6 mice, TH mice developed salt-sensitive hypertension and responded to a high salt diet with a significant rise in systolic blood pressure indicative of a blunted pressure-natriuresis relationship. These findings were evidenced by a decrease in total and fractional Na+ excretion and a right-shifted renal function curve with a reduced slope. This salt-sensitive hypertension correlated with changes in the Na/K-ATPase signaling. Specifically, Na/K-ATPase signaling was not able to be stimulated by HS due to the activated baseline protein carbonylation, phosphorylation of c-Src and ERK1/2. These findings support the emerging view that Na/K-ATPase signaling contributes to metabolic disease and suggest that malfunction of the Na/K-ATPase signaling may promote the development of salt-sensitive hypertension in obesity. The increased basal level of renal Na/K-ATPase-dependent redox signaling may be responsible for the development of salt-sensitive hypertension in polygenic obese TH mice.

Role of endothelin-1 in neointima formation after endothelial removal in rabbit carotid arteries

1994 ◽  
Vol 267 (6) ◽  
pp. H2259-H2267 ◽  
Author(s):  
H. Azuma ◽  
H. Hamasaki ◽  
Y. Niimi ◽  
T. Terada ◽  
O. Matsubara
Keyword(s):  
Time Course ◽  
Plasma Concentrations ◽  
Tissue Level ◽  
Nuclear Antigen ◽  
Control Group ◽  
Receptor Subtype ◽  
Neointima Formation ◽  
Subtype B ◽  
Selective Ligand

To investigate the role of local endothelin (ET)-1 in neointima formation, we performed a balloon denudation in the rabbit carotid artery. Four weeks after denudation, regeneration of endothelial cells was almost complete, and a marked intimal hyperplasia was observed. The tissue level of ET-1-like immunoreactivity was significantly increased even at 24 and 72 h after denudation and was 9.3 times higher than the control group in 4 wk. On the same time course, the proliferating cell nuclear antigen (PCNA)-positive cells clearly appeared. Receptor density values for 125I-ET-1 and 125I-IRL-1620 [ET-receptor subtype B (ETB)-selective ligand] bindings were significantly greater in the hyperplastic artery without changes in dissociation equilibrium constant values. The 125I-ET-1 binding sites not inhibited with BQ-123 [ET-receptor subtype A (ETA)-selective antagonist] were significantly increased in hyperplastic arteries. ETB receptors were more densely localized in the neointima. The chronic intravenous administration of BQ-123 at plasma concentrations sufficient to antagonize the ETA receptors had no effect on neointima formation and the appearance of PCNA-positive cells. We concluded from all results that ET-1 would be involved in neointima formation after endothelial removal and that the ETA receptors would not play a role in this process.

scholarly journals Protective Role of the Somatostatin Receptor Subtype 4 in the Indomethacin‐Induced Gastrointestinal Mucosal Injury Model

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Kata Csekő ◽  
Viktória Kormos ◽  
Ádám Horváth ◽  
Maria Sudalina ◽  
Natalia Iarushkina ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Mucosal Injury ◽  
Protective Role ◽  
Receptor Subtype ◽  
Injury Model

scholarly journals Renal Cortical Vasoconstriction Contributes to Development of Salt-Sensitive Hypertension after Angiotensin II Exposure

2001 ◽  
Vol 12 (11) ◽  
pp. 2263-2271
Author(s):  
MARTHA FRANCO ◽  
EDILIA TAPIA ◽  
JOSÉ SANTAMARÍA ◽  
IGNACIO ZAFRA ◽  
ROMEO GARCÍA-TORRES ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Plasma Flow ◽  
Critical Role ◽  
Progressive Increase ◽  
Tubulointerstitial Injury ◽  
High Salt Diet ◽  
Single Nephron ◽  
Glomerular Hemodynamics ◽  
Salt Sensitive Hypertension

Abstract. Rats that are administered angiotensin II (AngII) for 2 wk develop persistent salt-sensitive hypertension, which can be prevented by the immunosuppressor mycophenolate mofetil (MMF) given during the AngII infusion. This study examined the contribution of glomerular hemodynamics (GFR dynamics) in the post-AngII hypertensive response to a high-salt diet (HSD) and the effect of MMF treatment. During AngII administration, rats developed severe hypertension (systolic BP [SBP], 185 ± 3.9 mmHg), proteinuria, afferent and efferent vasoconstriction, and glomerular hypertension. Rats that received AngII+MMF showed similar responses to AngII; however, they developed lower proteinuria (P < 0.05). At 2 wk, AngII was withdrawn and SBP returned toward normal. Rats were then placed on an HSD (4% NaCl), resulting in a progressive increase in SBP (155 ± 8.2 mmHg at week 1 and 163 ± 4.5 mmHg at week 5). GFR dynamic alterations persisted after AngII was stopped, i.e., afferent and efferent vasoconstriction, decreased glomerular plasma flow and single-nephron GFR, and lower ultrafiltration coefficient. These changes correlated with the thickening of the afferent arteriole and with focal tubulointerstitial injury. In the AngII+MMF group, SBP remained unchanged throughout the HSD period (146 ± 2.3 mmHg at week 1 and 148 ± 4.4 mmHg at week 5) in association with less afferent arteriolar thickening and tubulointerstitial injury. Single-nephron GFR, glomerular plasma flow, efferent resistance, and ultrafiltration coefficient returned to normal with a significant reduction in afferent resistance. These results suggest a critical role of cortical vasoconstriction in salt-sensitive hypertension. The MMF-induced prevention of these changes suggests that immune mechanisms are involved in the vasoconstrictive response.

Polymorphisms in Cancer Susceptibility Genes XRCC1, RAD51 and TP53 and the Risk of Breast Cancer in Serbian Women

2016 ◽  
Vol 31 (3) ◽  
pp. 258-263 ◽  
Author(s):  
Ana M. Krivokuca ◽  
Milena R. Cavic ◽  
Emina J. Malisic ◽  
Jelena D. Rakobradovic ◽  
Daniela Kolarevic-Ivankovic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Hereditary Breast Cancer ◽  
Odds Ratio ◽  
Protective Role ◽  
Genotype Distribution ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
Young Breast Cancer

Background Thanks to immense improvements in technology over the past few decades, we have witnessed a major shift towards the idea that breast cancer results from a combined effect of multiple common alleles conferring low risk. This study investigates the role of 3 nonsynonymous SNPs in the DNA repair genes XRCC1 (R399Q), RAD51 (G135C) and TP53 (Arg72Pro) in breast cancer in Serbian women. Patients and Methods Cases of BRCA1/2-negative hereditary breast cancer (n = 52), sporadic breast cancer (n = 106) and age-matched cancer-free female controls (n = 104) were obtained from the Institute for Oncology and Radiology of Serbia's blood bank. Restriction fragment length polymorphism analysis was used for genotyping. Descriptive analyses included genotype and allelic frequencies; the odds ratio and 95% confidence interval were calculated as an estimate of the relative risk. Results A significant difference in QQ+RQ versus RR genotype distribution of XRCC1 was observed between hereditary breast cancer patients and cancer-free controls. The association was confirmed among young breast cancer patients from these high-risk families. The existence of 3 recessive alleles in the RAD51 and XRCC1 genotype combination showed an association with hereditary breast cancer. Odds ratio analysis indicated a strong protective role of the RAD51 GG + TP53 ArgArg + XRCC1 RR combined genotype against hereditary breast cancer negative for BRCA1/2 mutations. Conclusions The XRCC1 R399Q polymorphism showed an association with increased breast cancer risk in Serbia, especially in the hereditary form of the disease and in young breast cancer patients. Dominant alleles of RAD51, TP53 and XRCC1 combined genotypes indicated a strong protective role against hereditary breast cancer.

scholarly journals Renal medullary endothelin-1 is decreased in Dahl salt-sensitive rats

2011 ◽  
Vol 301 (2) ◽  
pp. R519-R523 ◽  
Author(s):  
Joshua S. Speed ◽  
Babbette LaMarca ◽  
Hunter Berry ◽  
Kathy Cockrell ◽  
Eric M. George ◽  
...  
Keyword(s):  
Sodium Intake ◽  
Renal Medulla ◽  
Receptor Expression ◽  
High Salt Diet ◽  
Salt Diet ◽  
High Sodium ◽  
Endothelin System ◽  
Chronic Infusion ◽  
Salt Sensitive Hypertension

Although it is well established that the renal endothelin (ET-1) system plays an important role in regulating sodium excretion and blood pressure through activation of renal medullary ETB receptors, the role of this system in Dahl salt-sensitive (DS) hypertension is unclear. The purpose of this study was to determine whether the DS rat has abnormalities in the renal medullary endothelin system when maintained on a high sodium intake. The data indicate that Dahl salt-resistant rats (DR) on a high-salt diet had a six-fold higher urinary endothelin excretion than in the DR rats with low Na+ intake (17.8 ± 4 pg/day vs. 112 ± 44 pg/day). In sharp contrast, urinary endothelin levels increased only twofold in DS rats in response to a high Na+ intake (13 ± 2 pg/day vs. 29.8 ± 5.5 pg/day). Medullary endothelin concentration in DS rats on a high-Na+ diet was also significantly lower than DR rats on a high-Na+ diet (31 ± 2.8 pg/mg vs. 70.9 ± 5 pg/mg). Furthermore, DS rats had a significant reduction in medullary ETB receptor expression compared with DR rats while on a high-Na+ diet. Finally, chronic infusion of ET-1 directly into the renal medulla blunted Dahl salt-sensitive hypertension. These data indicate that a decrease in medullary production of ET-1 in the DS rat could play an important role in the development of salt-sensitive hypertension observed in the DS rat.

Role of endothelin receptor subtype B(ET-B) in myocardial ischemia

Life Sciences ◽  
1994 ◽  
Vol 55 (23) ◽  
pp. 1833-1844 ◽  
Author(s):  
Carol A. Sargent ◽  
Eddie C.K. Liu ◽  
Chia-ching Chao ◽  
Maria L. Webb ◽  
Gary J. Grover
Keyword(s):  
Myocardial Ischemia ◽  
Receptor Subtype ◽  
Endothelin Receptor ◽  
Subtype B

Protective role of peroxiredoxin-4 in heart failure

2020 ◽  
Vol 134 (1) ◽  
pp. 71-72
Author(s):  
Naseer Ahmed ◽  
Masooma Naseem ◽  
Javeria Farooq
Keyword(s):  
Heart Failure ◽  
Cardiac Fibroblasts ◽  
Protective Role ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Total Antioxidant ◽  
Galectin 3 ◽  
Consequent Increase ◽  
And Oxidative Stress

Abstract Recently, we have read with great interest the article published by Ibarrola et al. (Clin. Sci. (Lond.) (2018) 132, 1471–1485), which used proteomics and immunodetection methods to show that Galectin-3 (Gal-3) down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. Authors concluded that ‘antioxidant activity of Prx-4 had been identified as a protein down-regulated by Gal-3. Moreover, Gal-3 induced a decrease in total antioxidant capacity which resulted in a consequent increase in peroxide levels and oxidative stress markers in cardiac fibroblasts.’ We would like to point out some results stated in the article that need further investigation and more detailed discussion to clarify certain factors involved in the protective role of Prx-4 in heart failure.

Parenting Behaviors and Anxiety in Young Adults

2015 ◽  
Vol 36 (3) ◽  
pp. 170-176 ◽  
Author(s):  
Erin N. Stevens ◽  
Joseph R. Bardeen ◽  
Kyle W. Murdock
Keyword(s):  
Effortful Control ◽  
Parenting Behaviors ◽  
Protective Role ◽  
Anxiety Symptoms ◽  
Interactive Effects ◽  
Parental Overprotection ◽  
High Control ◽  
Development Of Anxiety ◽  
The Relationship

Parenting behaviors – specifically behaviors characterized by high control, intrusiveness, rejection, and overprotection – and effortful control have each been implicated in the development of anxiety pathology. However, little research has examined the protective role of effortful control in the relation between parenting and anxiety symptoms, specifically among adults. Thus, we sought to explore the unique and interactive effects of parenting and effortful control on anxiety among adults (N = 162). Results suggest that effortful control uniquely contributes to anxiety symptoms above and beyond that of any parenting behavior. Furthermore, effortful control acted as a moderator of the relationship between parental overprotection and anxiety, such that overprotection is associated with anxiety only in individuals with lower levels of effortful control. Implications for potential prevention and intervention efforts which specifically target effortful control are discussed. These findings underscore the importance of considering individual differences in self-regulatory abilities when examining associations between putative early-life risk factors, such as parenting, and anxiety symptoms.

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