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Molecules (Basel, Switzerland) Apr 2022Urea transporter (UT) inhibitors are a class of promising novel diuretics that do not cause the imbalance of Na, K, Cl, and other electrolytes. In our previous studies,...
Urea transporter (UT) inhibitors are a class of promising novel diuretics that do not cause the imbalance of Na, K, Cl, and other electrolytes. In our previous studies, , a promising diuretic candidate inhibiting UT, was discovered and showed potent diuretic activities in rodents. Here, a sensitive liquid chromatography-tandem mass spectrometry method for the quantitation of in rat plasma, urine, feces, bile, and tissue homogenates was developed and validated to support the preclinical pharmacokinetic studies. The tissue distribution, excretion, and plasma protein binding were investigated in rats. After a single oral dose of at 25, 50, and 100 mg/kg, the drug exposure increased linearly with the dose. The drug accumulation was observed after multiple oral doses compared to a single dose. In the distribution study, exhibited a wide distribution to tissues with high blood perfusion, such as kidney, heart, lung, and spleen, and the lowest distribution in the brain and testis. The accumulative excretion rate of was 0.14%, 3.16%, and 0.018% in urine, feces, and bile, respectively. The plasma protein binding of was approximately 60% in rats and 40% in humans. This is the first study on the preclinical pharmacokinetic profiles of .
Topics: Animals; Chromatography, Liquid; Diuretics; Male; Membrane Transport Proteins; Rats; Rats, Sprague-Dawley; Urea; Urea Transporters
PubMed: 35458649
DOI: 10.3390/molecules27082451 -
Giornale Italiano Di Nefrologia :... Feb 2016Besides its religious importance, the Bible, because of its ancient origin represents a relevant witness of the way of life of the people mentioned in it. The Holy...
Besides its religious importance, the Bible, because of its ancient origin represents a relevant witness of the way of life of the people mentioned in it. The Holy Scripture is also the first text revealing the utility of plants for man, as natural sources of food, wood, fibers, oils and medicinal herbs. In the last 60 years, several distinguished botanists have attempted to identify the scientific names of the plants cited in the Bible. Nonetheless, these scholars have provided different lists of plants appearing in the Bible, none of which could be accepted as indisputable. The authors have combined their expertise to focus on the identification of the diuretic plants, through an historical analysis of the literature on this issue.
Topics: Bible; Diuretics; Ethnobotany; History, Ancient; Plants, Medicinal
PubMed: 26913893
DOI: No ID Found -
European Journal of Heart Failure Feb 2022Outpatient treatment for the worsening of signs and symptoms of heart failure (HF) is usually not incorporated in the main outcomes of HF trials. Patients with HF and a... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Outpatient treatment for the worsening of signs and symptoms of heart failure (HF) is usually not incorporated in the main outcomes of HF trials. Patients with HF and a preserved ejection fraction (HFpEF) may experience frequent episodes of outpatient worsening HF. The aim of this study was to evaluate the frequency, prognostic impact, and the effect of spironolactone on outpatient diuretic intensification (ODI), among 1767 patients enrolled in TOPCAT-Americas.
METHODS AND RESULTS
Time-updated Cox models and win ratio analysis. ODI was defined by a post-randomization loop diuretic dose increase or new initiation. The median follow-up was 2.9 years. At baseline, 1362 (77%) patients were taking loop diuretics. During the follow-up, 685 (38.8%) patients experienced ODI, which was associated with a higher risk of subsequent cardiovascular events and death [adjusted hazard ratio (HR) for HF hospitalization or cardiovascular death 1.67, 95% confidence interval (CI) 1.36-2.04; HR for cardiovascular death 2.17, 95% CI 1.64-2.87); and HR for all-cause mortality 1.75, 95% CI 1.41-2.16] (p < 0.001 for all outcomes). Adding ODI to the composite of HF hospitalization or cardiovascular death increased the event rate by three-fold in the placebo group (from 10.4 to 29.9 events per 100 person-years). Spironolactone treatment led to a 26% relative reduction of the extended composite of ODI or HF hospitalization or cardiovascular death (HR 0.74, 95% CI 0.65-0.85; p < 0.001) compared with a 16% relative reduction of HF hospitalization or cardiovascular death (HR 0.84, 95% CI 0.70-0.99; p = 0.044). Using win ratio provided similar estimates.
CONCLUSION
In HFpEF, ODI was frequent and independently associated with subsequent cardiovascular events. Spironolactone significantly reduced an extended composite outcome incorporating ODI.
Topics: Diuretics; Heart Failure; Hospitalization; Humans; Mineralocorticoid Receptor Antagonists; Outpatients; Stroke Volume
PubMed: 34755426
DOI: 10.1002/ejhf.2376 -
Pharmacology & Therapeutics 1980
Review
Topics: Age Factors; Aldosterone; Amiloride; Benzothiadiazines; Diuretics; Furosemide; Humans; Hypertension; Kidney Diseases; Kidney Tubules, Distal; Loop of Henle; Sodium; Sodium Chloride Symporter Inhibitors; Spironolactone
PubMed: 6997894
DOI: 10.1016/0163-7258(80)90025-x -
European Heart Journal Dec 1992This review concerns the modes of action of thiazides, loop- and potassium-sparing diuretics, with particular emphasis on their antihypertensive activity. Thiazide... (Comparative Study)
Comparative Study Review
This review concerns the modes of action of thiazides, loop- and potassium-sparing diuretics, with particular emphasis on their antihypertensive activity. Thiazide diuretics inhibit an enzyme in the basolateral cell membrane in the distal tubule, thus bringing about an impaired absorption and enhanced excretion of both Na+ and Cl- ions. The loss of Na+ ions is countered by the exchange from Na+ against K+, hence causing a loss of K+ ions. The renal excretion of Ca++ ions is impaired, that of Mg++ ions enhanced. Loop diuretics inhibit a carrier mechanism that enhances the inward transport into the tubular cells of Na+, K+ and Cl- ions as well as water. This process, which occurs in the thick ascending limb of Henle's loop, enhances the urinary excretions of these ions together with water and Ca++ and Mg++ ions. Potassium-sparing diuretics comprise two different categories. Triamterene and amiloride inhibit a local transport mechanism in the distal tubular cells which allows the influx of Na+ and its exchange against K+ or H+ ions. Concomitantly, the excretion of Na+, but not that of K+, ions is enhanced. Aldosterone antagonists inhibit the renal effects of aldosterone at the receptor level and impair the reabsorption of Na+ ions and water and their exchange against K+ ions. Despite detailed knowledge of the renal mode of action of the diuretics, the mechanism whereby they exert their antihypertensive activity is still uncertain. The initial reduction in plasma volume is accompanied by reduction in cardiac output and increased systemic vascular resistance. Continued treatment leads to a return to normal in cardiac output and a reduction in systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Diuretics; Hemodynamics; Humans; Hypertension; Kidney Tubules
PubMed: 1486901
DOI: 10.1093/eurheartj/13.suppl_g.2 -
Journal of Asian Natural Products... Aug 2021Three compounds with diuretic potential were identified from the 95% ethanol extract of (Christ) Ching. Among them, one was a new benzanilide named petiolide A (), and...
Three compounds with diuretic potential were identified from the 95% ethanol extract of (Christ) Ching. Among them, one was a new benzanilide named petiolide A (), and the other two were phenolic derivatives barbatic acid () and kaempferol (). Their structures were elucidated based on extensive spectral analyses and comparison with the literature data. The docking experiments of all compounds into the active site of the With-No-Lysine kinase 1 (WNK1) domain demonstrated that kaempferol () was the most effective component with diuretic potential for its comparative diuretic effect to that of an orally bioavailable WNK inhibitor WNK463 (docking score -10.99 vs -11.09).[Formula: see text].
Topics: Diuretics; Molecular Structure; Plant Extracts; Polypodiaceae
PubMed: 32602352
DOI: 10.1080/10286020.2020.1786065 -
ESC Heart Failure Dec 2022Given the various effects of sacubitril/valsartan in heart failure, a deeper understanding of atrial natriuretic peptide (ANP) actions is warranted. Natriuresis is a...
AIMS
Given the various effects of sacubitril/valsartan in heart failure, a deeper understanding of atrial natriuretic peptide (ANP) actions is warranted. Natriuresis is a fundamental action of ANP in acute heart failure (AHF), whereas the diuretic effect of ANP is different in each patient according to the diversity of renal response to ANP, which is affected by baseline plasma ANP status and deficiency of circulating ANP. Meanwhile, associations between other neuroendocrine hormones and the diuretic response to ANP are unclear. This study investigated the impact of pivotal neuroendocrine hormones on the diuretic effects of exogenous ANP, carperitide.
METHODS AND RESULTS
Plasma ANP, renin, aldosterone, and vasopressin levels and the diuretic effect of 0.0125 μg/kg/min of carperitide alone for the first 6 h were prospectively evaluated in 75 patients with AHF. Lower ANP levels were significantly associated with a greater diuretic response to exogenous ANP (r = -0.35, P = 0.002). Additionally, higher vasopressin levels were significantly related to the poor diuretic effects of exogenous ANP (r = -0.54, P < 0.001). Plasma ANP and vasopressin concentrations were not significantly correlated (r = 0.19, P = 0.10). Baseline systolic blood pressure, renal function, and prior use of loop diuretics did not predict the diuretic response to exogenous ANP, whereas vasopressin levels independently predicted a diuretic response to exogenous ANP (P < 0.001), as well as lower plasma ANP levels (P = 0.027).
CONCLUSIONS
Vasopressin status was significantly associated with the diuretic response to exogenous ANP in AHF, independent of plasma ANP status. The results may provide a better understanding of the actions of sacubitril/valsartan.
Topics: Humans; Atrial Natriuretic Factor; Diuretics; Heart Failure; Valsartan; Vasopressins; Neurosecretory Systems
PubMed: 36043451
DOI: 10.1002/ehf2.14083 -
Nephrology, Dialysis, Transplantation :... 1999
Review
Topics: Angiotensin-Converting Enzyme Inhibitors; Body Water; Diuretics; Drug Resistance; Heart Failure; Humans; Sodium
PubMed: 10463212
DOI: 10.1093/ndt/14.suppl_4.39 -
Trends in Pharmacological Sciences Nov 1988
Review
Topics: Animals; Diuretics; Humans; Receptors, Drug
PubMed: 3078079
DOI: 10.1016/0165-6147(88)90070-3 -
The Clinical Investigator Sep 1994
Review
Topics: Diuretics; Humans; Ion Transport; Kidney Diseases
PubMed: 7849454
DOI: 10.1007/BF00212997