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Handbook of Experimental Pharmacology 2022Activation of the kappa opioid receptor (KOR) induces antinociception, anti-pruritic activity, diuresis, sedation, and dysphoria. KOR agonist-induced diuresis is...
Activation of the kappa opioid receptor (KOR) induces antinociception, anti-pruritic activity, diuresis, sedation, and dysphoria. KOR agonist-induced diuresis is characterized as water diuresis, in which water excretion with urine is increased without altering electrolyte excretion. Both centrally and peripherally acting KOR agonists promote diuresis. KOR antagonists block KOR agonist-evoked diuresis suggesting that the diuretic effect is through activation of the KOR. Studies in different experimental animal species and in humans indicate that KOR agonists decrease antidiuretic hormone (ADH) secretion and release from the hypothalamus and posterior pituitary; decrease response to ADH in kidneys; increase renal sympathetic nerve activity; and increase adrenaline, noradrenaline, and dopamine release from the adrenal medulla. The therapeutic potentials of KOR agonists as water diuretics have been studied in animal models of cerebral edema due to ischemia and intracranial mass, hypertension, and cirrhosis. This chapter reviews characteristics, possible mechanisms, as well as therapeutic potentials of KOR agonist-induced diuresis.
Topics: Analgesics, Opioid; Animals; Diuresis; Dopamine; Humans; Narcotic Antagonists; Receptors, Opioid, kappa
PubMed: 33483878
DOI: 10.1007/164_2020_399 -
JACC. Heart Failure Jan 2024
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Heart Failure; Diabetes Mellitus, Type 2; Diuresis; Stroke Volume
PubMed: 37943224
DOI: 10.1016/j.jchf.2023.09.013 -
Circulation. Heart Failure Jul 2020
Topics: Heart Failure; Humans; Inflammation; Natriuresis; Natriuretic Peptides; Vasodilator Agents
PubMed: 32611204
DOI: 10.1161/CIRCHEARTFAILURE.120.007208 -
Current Drug Targets 2020Urea Transporters are a family of membrane channel proteins that facilitate the passive transport of urea across the plasma membrane. UTs are divided into two subgroups,... (Review)
Review
BACKGROUND
Urea Transporters are a family of membrane channel proteins that facilitate the passive transport of urea across the plasma membrane. UTs are divided into two subgroups, UT-A and UT-B. UT-As are primarily located in renal tubule epithelia and UT-Bs are highly expressed in renal descending vasa recta and extrarenal multiple tissues. Various urea transporter knockout mice exhibit low urine concentrating ability, which suggests that UTs are novel diuretic targets. With highthroughput screening of small molecule drug-like compound libraries, various potent UT inhibitors with IC50 at nanomolar level were identified. Furthermore, selective UT inhibitors exhibit diuretic activity without disturbing electrolyte and metabolism balance, which confirms the potential of UTs as diuretic targets and UT inhibitors as novel diuretics that do not cause electrolyte imbalance.
OBJECTIVE
This review article summarizes the identification and validation of urea transporter as a potential diuretic target and the discovery of small molecule UT inhibitors as a novel type of diuretics.
CONCLUSION
UTs are a potential diuretic target. UT inhibitors play significant diuresis and can be developed to diuretics without disturbing electrolyte balance.
Topics: Animals; Cell Line; Diuresis; Diuretics; Humans; Membrane Transport Proteins; Mice; Mice, Knockout; Small Molecule Libraries; Structure-Activity Relationship; Urea; Water-Electrolyte Balance; Urea Transporters
PubMed: 31782365
DOI: 10.2174/1389450120666191129101915 -
Surgical Laparoscopy, Endoscopy &... Oct 2022Feeding a ventral hernia repair (VHR) patient before the return of bowel function (ROBF) can lead to distention and emesis. Many patients spontaneously diurese after...
PURPOSE
Feeding a ventral hernia repair (VHR) patient before the return of bowel function (ROBF) can lead to distention and emesis. Many patients spontaneously diurese after surgery. We hypothesized that this auto-diuresis would signal ROBF.
MATERIALS AND METHODS
A total of 395 patients who underwent open, laparoscopic, or mixed VHR were evaluated for correlation between fluid status and ROBF or discharge. ROBF within 24 hours and discharge within 24 hours or 48 hours were used as outcome measures.
RESULTS
Patients remained an average 3.59 days after surgery in the hospital and the average ROBF was on day 2.99. The first shift of ≥700 mL of urine predicted ROBF ( P =0.03) and discharge ( P =0.04) within 24 hours. The first shift output of ≥500 mL predicted discharge within 48 hours ( P =0.02).
CONCLUSION
Auto-diuresis after surgery is correlated to ROBF and discharge. Accurate fluid measurement can predict bowel function and allow early diet and discharge.
Topics: Diuresis; Hernia, Ventral; Herniorrhaphy; Humans; Laparoscopy; Retrospective Studies
PubMed: 35960701
DOI: 10.1097/SLE.0000000000001083 -
Journal of Neurosurgery. Pediatrics Jun 2016
Topics: Acetazolamide; Diuresis; Humans; Neural Tube Defects
PubMed: 26824598
DOI: 10.3171/2015.9.PEDS15484 -
La Revue de Medecine Interne May 2023Post-Obstructive Diuresis (POD) is a polyuria that occurs following the release of an obstruction from the urinary tract that prevents the flow of urine. POD requires... (Review)
Review
Post-Obstructive Diuresis (POD) is a polyuria that occurs following the release of an obstruction from the urinary tract that prevents the flow of urine. POD requires prompt diagnosis to avoid complications. Although its pathophysiology is better understood, there is little scientific evidence for its treatment. Restoration of renal homeostasis requires correction of blood volume and electrolyte disturbances to prevent complications, which can be serious. In this article, we propose a synthesis of knowledge on the subject, as well as a management strategy.
Topics: Humans; Diuresis; Kidney; Polyuria; Physicians
PubMed: 36764894
DOI: 10.1016/j.revmed.2023.01.011 -
Acta Physiologica (Oxford, England) Feb 2022K balance in mammals relies on regulated renal K excretion matching unregulated fluctuating K intake. Upon a K rich meal, rapid and powerful K excretion is needed. Renal...
UNLABELLED
K balance in mammals relies on regulated renal K excretion matching unregulated fluctuating K intake. Upon a K rich meal, rapid and powerful K excretion is needed. Renal K secretion is stimulated by the increased tubular flow. We speculated that high K intake acutely increases urinary flow to stimulate K excretion.
METHODS
Mice were K challenged through diets or gavage. Post K loading urinary output, osmolarity, [K ] , [Na ] , plasma osmolarity, [copeptin] , [K ] , and [Na ] were measured. To locate the mechanism of K -induced diuresis in the glomerular/tubular system we measured creatinine excretion and assessed functional transport in isolated perfused TALs and CDs during an acute [K ] switch from 3.6 to 6.5 mM. Molecular adaptations of transport proteins involved in water reabsorption were investigated by immunoblotting.
RESULTS
(1) Mice switched from a 1% to 2% K diet increased diuresis within 12 hours and reciprocally reduced diuresis when switched from 1% to 0.01% K diet. (2) A single K gavage load, corresponding to 25%-50% of daily K intake, induced 100% increase in diuresis within 30 minutes. This occurred despite augmented plasma osmolarity and AVP synthesis. (3) K gavage did not change GFR. (4) In isolated perfused TALs, shifting [K ] from 3.6 to 6.5 mM did not affect AVP-induced NaCl transport. (5) In sharp contrast, in isolated perfused CDs, shifting [K ] from 3.6 to 6.5 mM markedly reduced CD AVP sensitivity, ie inhibited water absorption.
CONCLUSION
Dietary K loading induces a rapidly on-setting diuresis. The mechanism of K -induced diuresis involves desensitization of the CD to AVP.
Topics: Animals; Diet; Diuresis; Diuretics; Kidney; Mammals; Mice; Sodium
PubMed: 34984847
DOI: 10.1111/apha.13762 -
International Journal of Environmental... Apr 2023The present systematic review is aimed at evaluating the diuretic effects determined according to the natural mineral water consumption on healthy individuals. This... (Review)
Review
The present systematic review is aimed at evaluating the diuretic effects determined according to the natural mineral water consumption on healthy individuals. This systematic review has been performed following the guidelines of the PRISMA (preferred reporting items for systematic reviews and meta-analyses) Statement, investigating PubMed, Scopus, Web of Science and Cochrane Library from inception to November 2022. Studies performed both on animals and on humans were considered. After screening, a total of 12 studies have been identified. Of these, 11 studies were performed in Italy and 1 in Bulgaria. The time range of publication is very wide, ranging from 1962 to 2019 for human studies and from 1967 to 2001 for animal studies. All the included studies found an increase in diuresis determined according to the consumption of natural mineral water, in some cases after just one administration of the tested water. However, the quality of the studies is not so high, especially for the research conducted many years ago. Thus, it would be desirable to carry out new clinical studies using more appropriate methodological approaches and more refined methods of statistical data processing.
Topics: Humans; Mineral Waters; Diuresis; Bulgaria; Italy
PubMed: 37107810
DOI: 10.3390/ijerph20085527 -
The Journal of Pharmacology and... Aug 20228-Aminoguanine and 8-aminoguanosine (via metabolism to 8-aminoguanine) are endogenous 8-aminopurines that induce diuresis, natriuresis, and glucosuria by inhibiting...
8-Aminoguanine and 8-aminoguanosine (via metabolism to 8-aminoguanine) are endogenous 8-aminopurines that induce diuresis, natriuresis, and glucosuria by inhibiting purine nucleoside phosphorylase (PNPase); moreover, both 8-aminopurines cause antikaliuresis by other mechanisms. Because 8-aminoinosine and 8-aminohypoxanthine are structurally similar to 8-aminoguanosine and 8-aminoguanine, respectively, we sought to define their renal excretory effects. First, we compared the ability of 8-aminoguanine, 8-aminohypoxanthine, and 8-aminoinosine to inhibit recombinant PNPase. These compounds inhibited PNPase with a potency order of 8-aminoguanine > 8-aminohypoxanthine = 8-aminoinosine. Additional studies showed that 8-aminoinosine is a competitive substrate that is metabolized to a competitive PNPase inhibitor, namely 8-aminohypoxanthine. Administration of each 8-aminopurine (33.5 µmol/kg) reduced the guanine-to-guanosine and hypoxanthine-to-inosine ratios in urine, a finding confirming their ability to inhibit PNPase in vivo. All three 8-aminopurines induced diuresis, natriuresis, and glucosuria; however, the glucosuric effects of 8-aminohypoxanthine and 8-aminoinosine were less pronounced than those of 8-aminoguanine. Neither 8-aminohypoxanthine nor 8-aminoinosine altered potassium excretion, whereas 8-aminoguanine caused antikaliuresis. In vivo administration of 8-aminoinosine increased 8-aminohypoxanthine excretion, indicating that 8-aminohypoxanthine mediates, in part, the effects of 8-aminoinosine. Finally, 8-aminohypoxanthine was metabolized to 8-aminoxanthine by xanthine oxidase. Using ultraperformance liquid chromatography-tandem mass spectrometry, we identified 8-aminoinosine as an endogenous 8-aminopurine. In conclusion, 8-aminopurines have useful pharmacological profiles. To induce diuresis, natriuresis, glucosuria, and antikaliuresis, 8-aminoguanine (or its prodrug 8-aminoguanosine) would be preferred. If only diuresis and natriuresis, without marked glucosuria or antikaliuresis, is desired, 8-aminohypoxanthine or 8-aminoinosine might be useful. Finally, here we report the in vivo existence of another pharmacologically active 8-aminopurine, namely 8-aminoinosine. SIGNIFICANCE STATEMENT: Here, we report that a family of 8-aminopurines affects renal excretory function: effects that may be useful for treating multiple diseases including hypertension, heart failure, and chronic kidney disease. For diuresis and natriuresis accompanied by glucosuria and antikaliuresis, 8-aminoguanine (or its prodrug 8-aminoguanosine) would be useful; if only diuresis and natriuresis is called for, 8-aminohypoxanthine or 8-aminoinosine would be useful. Previously, we identified 8-aminoguanine and 8-aminoguanosine as endogenous 8-aminopurines; here, we extend the family of endogenous 8-aminopurines to include 8-aminoinosine.
Topics: Humans; Diuresis; Diuretics; Glycosuria; Natriuresis; Prodrugs; Purine-Nucleoside Phosphorylase
PubMed: 35609923
DOI: 10.1124/jpet.122.001221