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Molecules (Basel, Switzerland) Feb 2024Three new phenols (-), one new cyclohexanol (), two known phenols (-), and six known flavonoids (-) were isolated from the -butanol of the 75% ethanol extract of all...
Three new phenols (-), one new cyclohexanol (), two known phenols (-), and six known flavonoids (-) were isolated from the -butanol of the 75% ethanol extract of all plants of Miq. Among them, compound was named and described in its entirety for the first time, and compounds and were reported in for the first time. The structures of all compounds were confirmed using a comprehensive analysis of 1D and 2D NMR and HRESIMS data. Biological results show that compounds , , and exhibited potent diuretic activity. The modes of interaction between the selected compounds and the target diuretic-related WNK1 kinase were investigated in a preliminary molecular docking study. These results provided insight into the chemodiversity and potential diuretic activities of metabolites in .
Topics: Molecular Docking Simulation; Flavonoids; Antioxidants; Phenols; Plant Extracts
PubMed: 38474601
DOI: 10.3390/molecules29051092 -
Hipertension Y Riesgo Vascular Jun 2024Diuretics have been used for decades in the treatment of hypertension. Its efficacy has been demonstrated in numerous clinical trials. It is well known that the... (Review)
Review
Diuretics have been used for decades in the treatment of hypertension. Its efficacy has been demonstrated in numerous clinical trials. It is well known that the reduction in cardiovascular risk is a consequence of the reduction in blood pressure levels regardless of the drug used, but thiazide diuretics continue to be first-line drugs, especially in low doses and combined with other drugs. The debate on the advantages of using chlorthalidone or hydrochlorothiazide continues, however hydrochlorothiazide is drug most used and for which there is greater availability. The association with potassium-sparing diuretics increases the effectiveness and reduces the adverse reactions of thiazides. A new group of drugs, close to potassium-sparing diuretics, that antagonise aldosterone synthase are showing promising results as antihypertensives. There are no significant differences between men and women regarding the antihypertensive effect of thiazide diuretics.
PubMed: 38853071
DOI: 10.1016/j.hipert.2024.03.004 -
Federal Practitioner : For the Health... Dec 2023The 2017 American College of Cardiology/American Heart Association blood pressure guideline recommends chlorthalidone as the preferred thiazide diuretic. We aimed to...
BACKGROUND
The 2017 American College of Cardiology/American Heart Association blood pressure guideline recommends chlorthalidone as the preferred thiazide diuretic. We aimed to better understand thiazide prescribing patterns within the US Department of Veterans Affairs (VA).
METHODS
A retrospective analysis was conducted of patients with a prescription for hydrochlorothiazide (HCTZ), chlorthalidone, indapamide, or any combination products containing these from January 1, 2016, to January 21, 2022. The primary objective was to determine the utilization rates of each thiazide in the active cohort, assessed via χ test with Bonferroni correction. Secondary objectives included concomitant potassium or magnesium supplementation, blood pressure rates and control, and thiazide use from January 1, 2016, to December 31, 2021.
RESULTS
Of 628,994 active thiazide prescriptions, utilization rates differed significantly between thiazide groups ( < .001). Rates for HCTZ, chlorthalidone, and indapamide were 84.6%, 14.9%, and 0.5%, respectively. HCTZ use decreased from 90.2% to 83.5% ( < .001) and chlorthalidone use increased from 9.3% to 16.0% ( < .001). Between thiazide groups, rates of blood pressure control were not significantly different ( = .58). Potassium or magnesium supplementation was significantly different between groups ( < .001). The highest concomitant supplementation was with indapamide followed by chlorthalidone and HCTZ with rates of 27.1%, 22.6%, and 12.4%, respectively.
CONCLUSIONS
Despite guideline recommendations for chlorthalidone, HCTZ is the most prescribed thiazide diuretic within the VA. However, there was a significant trend toward increased chlorthalidone prescribing from 2016 to 2021. Application of these data may guide further research to increase guideline-recommended therapy.
PubMed: 38812589
DOI: 10.12788/fp.0439 -
Biomedicine & Pharmacotherapy =... Sep 2023The vasopressin system has emerged as a therapeutic focus for lowering portal hypertension and reducing splanchnic vasodilation in patients with refractory ascites....
Partial vasopressin 1a receptor agonism reduces portal hypertension and hyperaldosteronism and induces a powerful diuretic and natriuretic effect in rats with cirrhosis and ascites.
The vasopressin system has emerged as a therapeutic focus for lowering portal hypertension and reducing splanchnic vasodilation in patients with refractory ascites. Clinically available vasopressin agonists are limited by preferential selectivity for V1 receptors that also have steep concentration-response curves with potential risks of excess vasoconstriction and/or complete antidiuretic effects. OCE-205 is a novel, selective, partial V1a receptor agonist with mixed agonist/antagonist activity and no V2 receptor activation at therapeutic doses. We carried out two studies assessing the in vivo effects of OCE-205 in different rat models of cirrhosis and ascites. In a carbon tetrachloride rat cirrhosis model, OCE-205 administration produced a marked reduction in portal hypertension and hyperaldosteronism, along with robust diuretic and natriuretic effects. These effects were accompanied by marked decreases in ascites volume, with three of five animals experiencing total mobilization of ascites. There was no evidence of fluid overload or sodium or water retention, confirming OCE-205's lack of V2 receptor activity. In a second, corroborative study using a bile duct ligation rat model of ascites, OCE-205 produced significant decreases in ascites volume and body weight and a significant increase in urine volume versus vehicle. Urine sodium excretion increased significantly after the first administration of OCE-205 relative to vehicle; however, repeat administration over 5 days did not lead to hyponatremia. Thus, in separate in vivo models, the mixed agonist/antagonist OCE-205 demonstrated relevant and expected endpoint findings consistent with its known mechanism of action and in vitro pharmacology without apparent unwanted effects or nonspecific toxicities.
Topics: Rats; Animals; Diuretics; Natriuretic Agents; Ascites; Vasopressins; Liver Cirrhosis; Sodium; Receptors, Vasopressin; Hypertension, Portal; Hyperaldosteronism
PubMed: 37418980
DOI: 10.1016/j.biopha.2023.115116 -
Cells Nov 2023Type-2 Familial Partial Lipodystrophy (FPLD2), a rare lipodystrophy caused by mutations, is characterized by a loss of subcutaneous fat from the trunk and limbs and...
Type-2 Familial Partial Lipodystrophy (FPLD2), a rare lipodystrophy caused by mutations, is characterized by a loss of subcutaneous fat from the trunk and limbs and excess accumulation of adipose tissue in the neck and face. Several studies have reported that the mineralocorticoid receptor (MR) plays an essential role in adipose tissue differentiation and functionality. We previously showed that brown preadipocytes isolated from a FPLD2 patient's neck aberrantly differentiate towards the white lineage. As this condition may be related to MR activation, we suspected altered MR dynamics in FPLD2. Despite cytoplasmic MR localization in control brown adipocytes, retention of MR was observed in FPLD2 brown adipocyte nuclei. Moreover, overexpression of wild-type or mutated prelamin A caused GFP-MR recruitment to the nuclear envelope in HEK293 cells, while drug-induced prelamin A co-localized with endogenous MR in human preadipocytes. Based on in silico analysis and in situ protein ligation assays, we could suggest an interaction between prelamin A and MR, which appears to be inhibited by mineralocorticoid receptor antagonism. Importantly, the MR antagonist spironolactone redirected FPLD2 preadipocyte differentiation towards the brown lineage, avoiding the formation of enlarged and dysmorphic lipid droplets. Finally, beneficial effects on brown adipose tissue activity were observed in an FPLD2 patient undergoing spironolactone treatment. These findings identify MR as a new lamin A interactor and a new player in lamin A-linked lipodystrophies.
Topics: Humans; Lipodystrophy, Familial Partial; Adipocytes, Brown; Lamin Type A; Mineralocorticoid Receptor Antagonists; Spironolactone; Receptors, Mineralocorticoid; HEK293 Cells; Adipose Tissue, Brown
PubMed: 37998321
DOI: 10.3390/cells12222586 -
Frontiers in Cardiovascular Medicine 2023There is a growing interest in the evaluation of tricuspid regurgitation due to its increasing prevalence and detrimental impact on clinical outcomes. Historically, it... (Review)
Review
There is a growing interest in the evaluation of tricuspid regurgitation due to its increasing prevalence and detrimental impact on clinical outcomes. Historically, it has been coined the "forgotten" defect in the field of valvular heart disease due to the lack of effective treatments to improve prognosis. However, the development of percutaneous treatment techniques has led to a new era in its management, with promising results and diminished complication risk. In spite of these advances, a comprehensive exploration of the pathophysiological mechanisms is essential to establish clear indications and optimal timing for medical and percutaneous intervention. This review will address the most important aspects related to the diagnosis, pathophysiology and treatment of tricuspid regurgitation from a cardiorenal perspective, with a special emphasis on the interaction between right ventricular dysfunction and the development of hepatorenal congestion.
PubMed: 37859684
DOI: 10.3389/fcvm.2023.1255503 -
Biomedicines Aug 2023Soon after haemodialysis was introduced into clinical practice, a high risk of cardiac death was noted in end-stage renal disease. However, only in the last decade has... (Review)
Review
Soon after haemodialysis was introduced into clinical practice, a high risk of cardiac death was noted in end-stage renal disease. However, only in the last decade has it become clear that any renal injury, acute or chronic, is associated with high overall and cardiovascular lethality. The need for early recognition of kidney damage in cardiovascular pathology to assess risk and develop tactics for patient management contributed to the emergence of the concept of the "cardiorenal syndrome" (CRS). CRS is a pathophysiological disorder of the heart and kidneys in which acute or chronic dysfunction of one of these organs leads to acute or chronic dysfunction of the other. The beneficial effect of ultrafiltration as a component of renal replacement therapy (RRT) is due to the elimination of hyperhydration, which ultimately affects the improvement in cardiac contractile function. This review considers the theoretical background, current status of CRS, and future potential of RRT, focusing on the benefits of ultrafiltration as a therapeutic option.
PubMed: 37760806
DOI: 10.3390/biomedicines11092364 -
Polish Archives of Internal Medicine Dec 2023Resistant hypertension is defined as not achieving sufficient control of blood pressure (BP), that is, maintaining BP values equal to or above 140/90 mm Hg when using 3...
Resistant hypertension is defined as not achieving sufficient control of blood pressure (BP), that is, maintaining BP values equal to or above 140/90 mm Hg when using 3 antihypertensive drugs, including diuretics, properly combined and at maximum doses. The uncontrolled treated hypertension should be confirmed in out‑of‑office BP measurements, preferably with 24‑hour ambulatory BP monitoring. Demographic and clinical characteristics indicate that patients with resistant hypertension are older than the general population of patients with arterial hypertension and more often suffer from comorbidities. When resistant hypertension is suspected, it is necessary to assess whether optimal pharmacotherapy has been prescribed, including appropriate combinations of antihypertensive drugs and diuretics at appropriate doses. It is also important to exclude parallel use of drugs that may have unfavorable interactions leading to an increase in BP. A common cause of pseudoresistant hypertension is a patient's failure to comply with therapeutic recommendations, including a lack of lifestyle changes and nonadherence to the prescribed medication regimen. An important step in management of resistant hypertension is targeted screening with diagnostic tests for secondary hypertension. Expanding of the drug therapy beyond a 3‑drug regimen should include a mineralocorticoid receptor antagonist, in particular spironolactone. In selected patients, device‑based hypertension treatment might be considered.
Topics: Humans; Antihypertensive Agents; Hypertension; Diuretics; Blood Pressure; Spironolactone
PubMed: 38088817
DOI: 10.20452/pamw.16624 -
Annals of Medicine Dec 2023Hypokalaemia is a side-effect of diuretics. We aimed to use machine learning to identify features predicting hypokalaemia risk in hypertensive patients.
BACKGROUND
Hypokalaemia is a side-effect of diuretics. We aimed to use machine learning to identify features predicting hypokalaemia risk in hypertensive patients.
METHODS
Participants with hypertension in the United States National Health and Nutrition Examination Survey 1999-2018 were included for analysis. To select the most suitable algorithm, we tested and evaluated five machine learning algorithms commonly employed in epidemiological studies: Logistic Regression, k-Nearest Neighbor, Random Forest, Recursive Partitioning and Regression Trees, and eXtreme Gradient Boosting. These algorithms were accessed using a set of 38 screened features. We then selected the key hypokalaemia-associated features in the hypertension group and their cardiovascular diseases (CVD) subgroup using the SHapley Additive exPlanations (SHAP) values. Using SHAP values, the key features and their impact pattern on hypokalaemia risk were determined.
RESULTS
A total of 25,326 hypertensive participants were included for analysis, of whom 4,511 had known CVD. The Random Forest algorithm had the highest AUROC (hypertension dataset: 0.73 [95%CI, 0.71-0.76]; CVD subgroup: 0.72 [95%CI, 0.66-0.78]). Moreover, the nomogram based on the top twelve key features screened by random forest retained good performance: age, sex, race, poverty income ratio, body mass index, systolic and diastolic blood pressure, non-potassium-sparing diuretics use and duration, renin-angiotensin blockers use and duration, and CVD history in hypertension dataset; while in CVD subgroup, the additional key features were comorbid diabetes, education level, smoking status, and use of bronchodilators.
CONCLUSION
Our predictive model based on the random forest algorithm performed best among the tested and evaluated five algorithms. Hypokalaemia-associated key features have been identified in hypertensive patients and the subgroup with CVD. These findings from machine learning facilitate the development of artificial intelligence to highlight hypokalaemia risk in hypertension patients.
Topics: Humans; Artificial Intelligence; Hypokalemia; Nutrition Surveys; Hypertension; Algorithms; Cardiovascular Diseases; Machine Learning; Diuretics
PubMed: 37162442
DOI: 10.1080/07853890.2023.2209336 -
International Journal of Molecular... Dec 2023Diabetic cardiovascular complications are associated with up to 50% mortality, and current therapies are not effective enough. Renin-angiotensin-aldosterone system...
Diabetic cardiovascular complications are associated with up to 50% mortality, and current therapies are not effective enough. Renin-angiotensin-aldosterone system inhibitors (RAASis) are the standard of care for diabetic patients with hypertension and albuminuria. Based on our previous studies reporting the renoprotective effects of low-dose RAASis, here, we hypothesized that low-dose RAASi treatment has cardioprotective and antifibrotic benefits in type 1 diabetes mellitus (T1DM). After five weeks of T1DM, adult male Wistar rats received low doses of ramipril, losartan, or eplerenone for two weeks. Heart rate, blood pressure, and pulse wave velocity (PWV) were recorded. Aortic intima-media thickness (IMT), collagen accumulation, and myocardial fibrosis were assessed. All RAASis reduced PWV elevation, prevented the progression of myocardial fibrosis, and normalized B-type natriuretic peptide, troponin I, and fibroblast growth factor 23 levels without affecting blood pressure. Interestingly, only eplerenone reversed the decline in Klotho levels and reduced IMT and fibrosis in the media of the aorta. Our comparative analysis suggests that mineralocorticoid receptor antagonists, particularly eplerenone, may offer superior efficacy in halting both the arterial and the myocardial injuries in T1DM compared to angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers.
Topics: Animals; Male; Rats; Cardiomyopathies; Carotid Intima-Media Thickness; Diabetes Complications; Diabetes Mellitus, Type 1; Eplerenone; Fibrosis; Pulse Wave Analysis; Rats, Wistar; Renin-Angiotensin System
PubMed: 38069366
DOI: 10.3390/ijms242317043