ANO1 taking center stage: blood pressure regulation in SHRs.
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ABSTRACT:
SUBMITTER: Li Q
PROVIDER: S-EPMC4819994 | biostudies-literature | 2015 May
REPOSITORIES: biostudies-literature
Publications
ANO1 taking center stage: blood pressure regulation in SHRs.
Journal of molecular and cellular cardiology 20150326
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Project description:Gastrodin is a bioactive compound extracted from traditional Chinese medicine, Gastrodia elata Bl. It has a definite effect on reducing blood pressure in hypertensive patients. However, the mechanisms of gastrodin in lowering blood pressure still remain unclear. In this study, 4 weeks of administration of gastrodin (100 mg/kg/d intraperitoneally injected) decreased the systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) (190.2 ± 8.9 versus 169.8 ± 6.4, P < 0.01). Among SHRs receiving gastrodin treatment, angiotensin II (Ang II) and aldosterone (ALD) in serum were significantly decreased (2022.1 ± 53.0 versus 1528.7 ± 93.9, 213.33 ± 35.17 versus 179.65 ± 20.31, and P < 0.01, P < 0.05, resp.) and dramatically downregulated expression of angiotensin type 1 receptor (AT1R) (4.9 ± 0.9 versus 2.6 ± 0.9, P < 0.05) in myocardium in both mRNA and protein levels compared with their corresponding groups without gastrodin treatment. Additionally, gastrodin increased the mRNA expression (0.18 ± 0.07 versus 0.82 ± 0.10, P < 0.01) and protein synthesis (0.40 ± 0.10 versus 0.34 ± 0.10, P < 0.01) of peroxisome proliferator-activated receptor γ (PPARγ) in myocardium tissues. Overall, our data demonstrated that gastrodin was able to decrease the SBP in SHR. Furthermore, this study showed that gastrodin intervened with the renin-angiotensin-aldosterone system (RAAS) and PPARγ effectively, which indicates its antihypertensive mechanism.
| S-EPMC4637485 | biostudies-literature
Project description:The present study investigated the effects of electroacupuncture on blood pressure in spontaneously hypertensive rats (SHRs) by regulating the immune balance of T helper 17 cells (Th17 cells) and regulatory T cells (Treg cells). This study investigated the role of electroacupuncture in the immune balance of SHRs using Western blot, flow cytometry, and ELISA techniques. Electroacupuncture significantly improved blood pressure, downregulated the expression of RORγt, and upregulated the expression of Foxp3, reduced the production of Th17 cells, promoted the production of Treg cells, reduced the secretion of IL-6 and IL-17, and increased the secretion of TGF-β1 and IL-10. These findings suggest that electroacupuncture therapy effectively improved the systolic blood pressure of SHRs, and its mechanism may be related to promotion of the immune balance between Th17 and Treg.
| S-EPMC7366219 | biostudies-literature
Project description:ObjectivesTo determine the association of fragmented ambulatory health care with uncontrolled blood pressure (BP) and apparent treatment-resistant hypertension (aTRH) among older adults taking antihypertensive medication, overall and by race and gender.Study designCross-sectional study using data from 2868 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants 66 years and older who completed a study examination in 2013-2016, had Medicare fee-for-service coverage, and were taking antihypertensive medication.MethodsWe used logistic regression to analyze the association of fragmented health care with uncontrolled BP and aTRH. Fragmented health care was operationalized as a reversed Bice-Boxerman Index score in the 75th percentile or higher, calculated using the number of ambulatory providers and health care visits in the year preceding the study examination. Uncontrolled BP was defined by systolic BP of at least 140 mm Hg or diastolic BP of at least 90 mm Hg. aTRH was defined by taking 3 or more classes of antihypertensive medication with uncontrolled BP or 4 or more classes with controlled BP.ResultsThe overall adjusted odds ratios (95% CIs) for uncontrolled BP, aTRH with controlled BP, and aTRH with uncontrolled BP associated with fragmented health care were 1.10 (0.89-1.37), 1.08 (0.80-1.47), and 1.32 (0.96-1.81), respectively. Fragmented health care was not associated with uncontrolled BP or aTRH among White participants, women, or men. Among Black participants, the odds ratio (95% CI) associated with fragmented health care was 1.21 (0.81-1.82) for uncontrolled BP, 1.22 (0.72-2.07) for aTRH with controlled BP, and 1.82 (1.07-3.11) for aTRH with uncontrolled BP.ConclusionsFragmented health care may increase the likelihood of aTRH with uncontrolled BP among older Black adults taking antihypertensive medication.
| S-EPMC9358913 | biostudies-literature
Project description:We investigated the relationship between blood pressure (BP) and mortality in patients taking antihypertensive medications in the Korean using data from the 2007-2015 Korean National Health and Nutrition Examination Surveys. A total of 6601 patients aged 30-74 years were included. Systolic BP (SBP) and diastolic BP (DBP) were both divided into four groups as follows: SBP < 120, 120 ≤ SBP ≤ 129 130 ≤ SBP ≤ 139, and SBP ≥ 140; DBP < 70, 70 ≤ DBP ≤ 79, 80 ≤ DBP ≤ 89, and DBP ≥ 90. The survival rates and hazard ratios were evaluated using Kaplan-Meier curves and multivariable Cox regression analyses. To evaluate the predictability of all-cause mortality according to SBP and/or DBP, we calculated Harrell's concordance-index. The lowest DBP group had a high risk of mortality regardless of the SBP status. The group with DBP < 70 mm Hg and SBP ≥ 140 mm Hg showed the highest mortality. The discriminatory ability calculated using Harrell's C-indexes was greater for the combination of SBP and DBP compared to DBP or SBP alone. These results suggest that it is more effective to simultaneously evaluate the effect of SBP and DBP to predict mortality; clinicians should manage DBP < 70 mm Hg when treating hypertensive patients.
| S-EPMC8029854 | biostudies-literature
Project description:Background and objectivesRecent guidelines recommend out-of-clinic BP measurements.Design, setting, participants, & measurementsWe compared the prevalence of BP phenotypes between 561 black patients, with and without CKD, taking antihypertensive medication who underwent ambulatory BP monitoring at baseline (between 2000 and 2004) in the Jackson Heart Study. CKD was defined as an albumin-to-creatinine ratio ≥30 mg/g or eGFR <60 ml/min per 1.73 m2. Sustained controlled BP was defined by BP at goal both inside and outside of the clinic and sustained uncontrolled BP as BP above goal both inside and outside of the clinic. Masked uncontrolled hypertension was defined by controlled clinic-measured BP with uncontrolled out-of-clinic BP.ResultsCKD was associated with a higher multivariable-adjusted prevalence ratio for uncontrolled versus controlled clinic BP (prevalence ratio, 1.44; 95% CI, 1.02 to 2.02) and sustained uncontrolled BP versus sustained controlled BP (prevalence ratio, 1.66; 95% CI, 1.16 to 2.36). There were no statistically significant differences in the prevalence of uncontrolled daytime or nighttime BP, nondipping BP, white-coat effect, and masked uncontrolled hypertension between participants with and without CKD after multivariable adjustment. After multivariable adjustment, reduced eGFR was associated with masked uncontrolled hypertension versus sustained controlled BP (prevalence ratio, 1.42; 95% CI, 1.00 to 2.00), whereas albuminuria was associated with uncontrolled clinic BP (prevalence ratio, 1.76; 95% CI, 1.20 to 2.60) and sustained uncontrolled BP versus sustained controlled BP (prevalence ratio, 2.02; 95% CI, 1.36 to 2.99).ConclusionsThe prevalence of BP phenotypes defined using ambulatory BP monitoring is high among adults with CKD taking antihypertensive medication.
| S-EPMC7133126 | biostudies-literature
Project description:BackgroundAlthough recent hypertension guidelines recommend home blood pressure (HBP) monitoring, its effect in clinical practice is not well known. This study aimed to identify current HBP measurement status and obstacles and their efficacy on blood pressure (BP) control.MethodsSixty-three intervention and 61 control centers with 2483 (mean age: 58.0 years, 56.0% male) drug-naïve stage 2 hypertensive patients or patients requiring second anti-hypertensive medications were included. The intervention group was instructed to measure HBP twice a day for 7 days from the scheduled visit at 4, 8, and 12 weeks.ResultsAt the end of 12 weeks, 842 (68.7%) and 807 (64.15%) patients of the control and intervention groups, respectively, achieved a target BP. The odds ratio (OR) for improving BP control of HBP was 0.836 (95% confidence interval [CI]: 0.694-1.007). Among intervention group, clinic BP of the subgroup those measured their HBP at least once well controlled compared to subgroup those not measured their HBP at all (OR 1.602, 95% CI: 1.182-2.172). Only 19.17% (n = 476) had a home sphygmomanometer, and among those, 26.89% measured their BP at least once a week and 34.87% did not measure the BP at all. The obstacles of HBP measurement were lack of awareness of its importance (40.83%), lack of confidence on how to measure BP and maintain the measurement (37.04%), and difficulty in selecting an appropriate device (14.41%).ConclusionsHBP measurement alone did not improve BP control, but better compliance with the HBP measurement resulted in improved BP control.Trial registrationClinicalTrials, NCT03254914 , Registered 21 August 2017.
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Project description:Most bodily functions vary over the course of a 24h day. Circadian rhythms in body temperature, sleep-wake cycles, metabolism, and blood pressure (BP) are just a few examples. These circadian rhythms are controlled by the central clock in the suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral clocks located throughout the body. Light and food cues entrain these clocks to the time of day and this synchronicity contributes to the regulation of a variety of physiological processes with effects on overall health. The kidney, brain, nervous system, vasculature, and heart have been identified through the use of mouse models and clinical trials as peripheral clock regulators of BP. The dysregulation of this circadian pattern of BP, with or without hypertension, is associated with increased risk for cardiovascular disease. The mechanism of this dysregulation is unknown and is a growing area of research. In this review, we highlight research of human and mouse circadian models that has provided insight into the roles of these molecular clocks and their effects on physiological functions. Additional tissue-specific studies of the molecular clock mechanism are needed, as well as clinical studies including more diverse populations (different races, female patients, etc.), which will be critical to fully understand the mechanism of circadian regulation of BP. Understanding how these molecular clocks regulate the circadian rhythm of BP is critical in the treatment of circadian BP dysregulation and hypertension.
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Project description:Hypertension (high blood pressure) is a major public health problem affecting more than a billion people worldwide with complications, including stroke, heart failure and kidney failure. The regulation of blood pressure is multifactorial reflecting genetic susceptibility, in utero environment and external factors such as obesity and salt intake. In keeping with Arthur Guyton's hypothesis, the kidney plays a key role in blood pressure control and data from clinical studies; physiology and genetics have shown that hypertension is driven a failure of the kidney to excrete excess salt at normal levels of blood pressure. There is a number of rare Mendelian blood pressure syndromes, which have shed light on the molecular mechanisms involved in dysregulated ion transport in the distal kidney. One in particular is Familial hyperkalemic hypertension (FHHt), an autosomal dominant monogenic form of hypertension characterised by high blood pressure, hyperkalemia, hyperchloremic metabolic acidosis, and hypercalciuria. The clinical signs of FHHt are treated by low doses of thiazide diuretic, and it mirrors Gitelman syndrome which features the inverse phenotype of hypotension, hypokalemic metabolic alkalosis, and hypocalciuria. Gitelman syndrome is caused by loss of function mutations in the thiazide-sensitive Na/Cl cotransporter (NCC); however, FHHt patients do not have mutations in the SCL12A3 locus encoding NCC. Instead, mutations have been identified in genes that have revealed a key signalling pathway that regulates NCC and several other key transporters and ion channels in the kidney that are critical for BP regulation. This is the WNK kinase signalling pathway that is the subject of this review.
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Project description:Blood pressure (BP) is determined by several physiological factors that are regulated by a range of complex neural, endocrine, and paracrine mechanisms. This study examined a collection of 198 human genes related to BP regulation, in the biological processes and functional prisms, as well as gene expression in organs and tissues. This was made in conjunction with an orthology analysis performed in 19 target organisms along the phylogenetic tree. We have demonstrated that transport and signaling, as well as homeostasis in general, are the most prevalent biological processes associated with BP gene orthologs across the examined species. We showed that these genes and their orthologs are expressed primarily in the kidney and adrenals of complex organisms (e.g., high order vertebrates) and in the nervous system of low complexity organisms (e.g., flies, nematodes). Furthermore, we have determined that basic functions such as ion transport are ancient and appear in all organisms, while more complex regulatory functions, such as control of extracellular volume emerged in high order organisms. Thus, we conclude that the complex system of BP regulation evolved from simpler components that were utilized to maintain specific homeostatic functions that play key roles in existence and survival of organisms.
| S-EPMC8145682 | biostudies-literature
Project description:20-Hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE) is a cytochrome P450 (CYP)-derived omega-hydroxylation metabolite of arachidonic acid. 20-HETE has been shown to play a complex role in blood pressure regulation. In the kidney tubules, 20-HETE inhibits sodium reabsorption and promotes natriuresis, thus, contributing to antihypertensive mechanisms. In contrast, in the microvasculature, 20-HETE has been shown to play a pressor role by sensitizing smooth muscle cells to constrictor stimuli and increasing myogenic tone, and by acting on the endothelium to further promote endothelial dysfunction and endothelial activation. In addition, 20-HETE induces endothelial angiotensin-converting enzyme, thus, setting forth a potential feed forward prohypertensive mechanism by stimulating the renin-angiotensin-aldosterone system. With the advancement of gene sequencing technology, numerous polymorphisms in the regulatory coding and noncoding regions of 20-HETE-producing enzymes, CYP4A11 and CYP4F2, have been associated with hypertension. This in-depth review article discusses the biosynthesis and function of 20-HETE in the cardiovascular system, the pharmacological agents that affect 20-HETE action, and polymorphisms of CYP enzymes that produce 20-HETE and are associated with systemic hypertension in humans.
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