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Molecules (Basel, Switzerland) Jul 2021Neuropeptide Y (NPY) acts via multiple receptor subtypes termed Y, Y and Y. While Y receptor-mediated effects, e.g., in the vasculature, are often sensitive to...
Neuropeptide Y (NPY) acts via multiple receptor subtypes termed Y, Y and Y. While Y receptor-mediated effects, e.g., in the vasculature, are often sensitive to inhibitors of L-type Ca channels such as nifedipine, little is known about the role of such channels in Y-mediated effects such as diuresis and natriuresis. Therefore, we explored whether nifedipine affects NPY-induced diuresis and natriuresis. After pre-treatment with nifedipine or vehicle, anesthetized rats received infusions or bolus injections of NPY. Infusion NPY (1 µg/kg/min) increased diuresis and natriuresis, and this was attenuated by intraperitoneal injection of nifedipine (3 µg/kg). Concomitant decreases in heart rate and reductions of renal blood flow were not attenuated by nifedipine. Bolus injections of NPY (0.3, 1, 3, 10 and 30 μg/kg) dose-dependently increased mean arterial pressure and renovascular vascular resistance; only the higher dose of nifedipine (100 μg/kg/min i.v.) moderately inhibited these effects. We conclude that Y-mediated diuresis and natriuresis are more sensitive to inhibition by nifedipine than Y-mediated renovascular effects. Whether this reflects a general sensitivity of Y receptor-mediated responses or is specific for diuresis and natriuresis remains to be investigated.
Topics: Animals; Calcium Channel Blockers; Male; Natriuresis; Neuropeptide Y; Nifedipine; Rats; Rats, Wistar; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Receptors, Neuropeptide Y
PubMed: 34361613
DOI: 10.3390/molecules26154460 -
Journal of Veterinary Internal Medicine May 2021Diuretic braking during furosemide continuous rate infusion (FCRI) curtails urine production.
BACKGROUND
Diuretic braking during furosemide continuous rate infusion (FCRI) curtails urine production.
HYPOTHESIS
Renin-angiotensin-aldosterone system (RAAS) activation mediates braking, and RAAS inhibition will increase urine production.
ANIMALS
Ten healthy purpose-bred male dogs.
METHODS
Dogs received placebo, benazepril, or benazepril and spironolactone PO for 3 days before a 5-hour FCRI (0.66 mg/kg/h) in a 3-way, randomized, blinded, cross-over design. Body weight (BW), serum creatinine concentration (sCr), serum electrolyte concentrations, PCV, and total protein concentration were measured before PO medications, at hours 0 and 5 of FCRI, and at hour 24. During the FCRI, water intake, urine output, urine creatinine concentration, and urine electrolyte concentrations were measured hourly. Selected RAAS components were measured before and after FCRI. Variables were compared among time points and treatments.
RESULTS
Diuretic braking and urine production were not different among treatments. Loss of BW, hemoconcentration, and decreased serum chloride concentration occurred during FCRI with incomplete recovery at hour 24 for all treatments. Although unchanged during FCRI, sCr increased and serum sodium concentration decreased at hour 24 for all treatments. Plasma aldosterone and angiotensin-II concentrations increased significantly at hour 5 for all treatments, despite suppressed angiotensin-converting enzyme activity during benazepril background treatment.
CONCLUSIONS
The neurohormonal profile during FCRI supports RAAS mediation of diuretic braking in this model. Background treatment with benazepril with or without spironolactone did not mitigate braking, but was well tolerated. Delayed changes in sCr and serum sodium concentration and incomplete recovery of hydration indicators caused by furosemide hold implications for clinical patients.
Topics: Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Diuresis; Diuretics; Dogs; Furosemide; Male; Renin-Angiotensin System; Spironolactone
PubMed: 33713485
DOI: 10.1111/jvim.16097 -
American Journal of Physiology. Renal... Nov 2018The antidiuretic hormone vasopressin (VP) is produced by the hypothalamus and is stored and secreted from the posterior pituitary. VP acts via VP type 2 receptors (V2Rs)... (Review)
Review
The antidiuretic hormone vasopressin (VP) is produced by the hypothalamus and is stored and secreted from the posterior pituitary. VP acts via VP type 2 receptors (V2Rs) on the basolateral membrane of principal cells of the collecting duct (CD) to regulate fluid permeability. The VP-evoked endocrine pathway is essential in determining urine concentrating capability. For example, a defect in any component of the VP signaling pathway can result in polyuria, polydipsia, and hypotonic urine, collectively termed diabetes insipidus (DI). A lack of VP production precipitates central diabetes insipidus (CDI), which can be managed effectively by VP supplementation. A majority of cases of nephrogenic diabetes insipidus (NDI) result from V2R mutations that impair receptor sensitivity. No specific therapy is currently available for management of NDI. Evidence is evolving that (pro)renin receptor (PRR), a newly identified member of the renin-angiotensin system, is capable of regulating VP production and action. As such, PRR should be considered strongly as a therapeutic target for treating CDI and NDI. The current review will summarize recent advances in understanding the physiology of renal and central PRR as it relates to the two types of DI.
Topics: Animals; Antidiuretic Agents; Diabetes Insipidus; Diuresis; Genetic Predisposition to Disease; Humans; Kidney; Mutation; Phenotype; Receptors, Cell Surface; Receptors, Vasopressin; Renin-Angiotensin System; Vasopressins; Prorenin Receptor
PubMed: 30019932
DOI: 10.1152/ajprenal.00266.2018 -
Night-time diuresis pattern in children with and without primary monosymptomatic nocturnal enuresis.Journal of Pediatric Urology May 2019Night-time polyuria as the dominating pathophysiological mechanism for primary monosymptomatic nocturnal enuresis (PMNE) has been put in question with nocturnal detrusor... (Comparative Study)
Comparative Study
INTRODUCTION
Night-time polyuria as the dominating pathophysiological mechanism for primary monosymptomatic nocturnal enuresis (PMNE) has been put in question with nocturnal detrusor overactivity and high arousal thresholds as alternatives. An earlier finding of night-time polyuria in 12% of healthy non-enuretic schoolchildren underscores that excessive night-time diuresis per se is unlikely the major cause of PMNE.
OBJECTIVE
The objective of this study was to compare the night-time diuresis pattern in children with and without PMNE and to evaluate the role of night-time polyuria in provoking enuretic episodes in children with PMNE.
STUDY DESIGN
Night-time diuresis pattern was recorded in 27 children with PMNE, aged 6-15 years, and 29 non-enuretic children, aged 6-13 years. Using a portable ultrasound recorder, the bladder volume was estimated at 15-min intervals for at least three nights with the child sleeping in its own bed at home. The volume of enuretic episodes was controlled using preweighed diapers. All voids were registered by time and volume. Diuresis during night time was estimated from the slope of regression lines fitted to ultrasound recording points. Mean night-time diuresis was calculated from total urine production during the night and time interval from the last void before bedtime to the first morning void.
RESULTS
Night-time bladder filling pattern was recorded from 189 nights, giving 149 interpretable patterns for analysis (77 children with PMNE and 72 dry children). The night-time diuresis pattern was similar for children with or without PMNE, showing large variability between different nights of the same child. Most nights displayed a smooth bladder filling at constant low rate, whereas other nights showed an early phase with high diuresis followed by a longer period of low diuresis with no difference between the two groups.
DISCUSSION
Night-time diuresis has been non-invasively monitored in children while asleep in their own beds at home. The pattern of night-time diuresis varies considerably between different nights of the same child, with no obvious differences in any diuresis parameters between children with or without PMNE.
CONCLUSION
Non-enuretic children have similar diuresis pattern and maximal night-time diuresis values as children with PMNE, making it unlikely that PMNE is caused by night-time polyuria per se (Summary figure). Delayed maturation of sleep mechanisms such as decreased arousability or sleep inhibition of the micturition reflex is more likely to be the main etiology for enuresis.
Topics: Adolescent; Child; Diuresis; Female; Humans; Male; Nocturnal Enuresis
PubMed: 30857839
DOI: 10.1016/j.jpurol.2019.02.002 -
Circulation. Heart Failure Jan 2024The use of urinary sodium to guide diuretics in acute heart failure is recommended by experts and the most recent European Society of Cardiology guidelines. However,...
BACKGROUND
The use of urinary sodium to guide diuretics in acute heart failure is recommended by experts and the most recent European Society of Cardiology guidelines. However, there are limited data to support this recommendation. The ENACT-HF study (Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure) investigated the feasibility and efficacy of a standardized natriuresis-guided diuretic protocol in patients with acute heart failure and signs of volume overload.
METHODS
ENACT-HF was an international, multicenter, open-label, pragmatic, 2-phase study, comparing the current standard of care of each center with a standardized diuretic protocol, including urinary sodium to guide therapy. The primary end point was natriuresis after 1 day. Secondary end points included cumulative natriuresis and diuresis after 2 days of treatment, length of stay, and in-hospital mortality. All end points were adjusted for baseline differences between both treatment arms.
RESULTS
Four hundred one patients from 29 centers in 18 countries worldwide were included in the study. The natriuresis after 1 day was significantly higher in the protocol arm compared with the standard of care arm (282 versus 174 mmol; adjusted mean ratio, 1.64; <0.001). After 2 days, the natriuresis remained higher in the protocol arm (538 versus 365 mmol; adjusted mean ratio, 1.52; <0.001), with a significantly higher diuresis (5776 versus 4381 mL; adjusted mean ratio, 1.33; <0.001). The protocol arm had a shorter length of stay (5.8 versus 7.0 days; adjusted mean ratio, 0.87; =0.036). In-hospital mortality was low and did not significantly differ between the 2 arms (1.4% versus 2.0%; =0.852).
CONCLUSIONS
A standardized natriuresis-guided diuretic protocol to guide decongestion in acute heart failure was feasible, safe, and resulted in higher natriuresis and diuresis, as well as a shorter length of stay.
Topics: Humans; Diuretics; Natriuresis; Heart Failure; Diuresis; Sodium; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 38179728
DOI: 10.1161/CIRCHEARTFAILURE.123.011105 -
Andes Pediatrica : Revista Chilena de... Feb 2021Hyponatremia is a common hydroelectrolytic disorder in pediatric patients with advanced cirrhosis. This complication is related to the alteration in the renal capacity... (Review)
Review
Hyponatremia is a common hydroelectrolytic disorder in pediatric patients with advanced cirrhosis. This complication is related to the alteration in the renal capacity to eliminate free water with solutes such as sodium, which leads to disproportionate water retention, a condition known as dilutional hyponatremia. The main pathogenic factors are the non-osmotic secretion of antidiuretic hormone and the activation of the renin-angiotensin-aldosterone axis and the sympathetic nervous system. Given that hyponatremia in cirrhosis is associated with an increase in morbidity and mortality, the objective of this review is to propose a systematic approach, based on the level of serum sodium, assessment of hemodynamic status and diuresis, which allows precise modifications that minimize negative impacts on survival and neurological sequelae.
Topics: Child; Diuresis; Hemodynamics; Humans; Hyponatremia; Liver Cirrhosis; Sodium
PubMed: 34106192
DOI: 10.32641/andespediatr.v92i1.2669 -
European Radiology May 2023Increased detection of prostate cancer (PCa) recurrences using [Ga]Ga-PSMA-11 PET/CT has been reported by adding forced diuresis or late-phase imaging to the standard...
OBJECTIVES
Increased detection of prostate cancer (PCa) recurrences using [Ga]Ga-PSMA-11 PET/CT has been reported by adding forced diuresis or late-phase imaging to the standard protocol. However, the combination of these procedures in the clinical setting is still not standardized.
METHODS
One hundred prospectively recruited biochemical recurrent PCa patients were restaged with dual-phase [Ga]Ga-PSMA-11 PET/CT from September 2020 to October 2021. All patients received a standard scan (60 min), followed by diuretics (140 min) and a late-phase abdominopelvic scan (180 min). PET readers with low (n = 2), intermediate (n = 2), or high (n = 2) experience rated (i) standard and (ii) standard + forced diuresis late-phase images in a stepwise fashion according to E-PSMA guidelines, scoring their level of confidence. Study endpoints were (i) accuracy against a composite reference standard, (ii) reader's confidence level, and (iii) interobserver agreement.
RESULTS
Forced diuresis late-phase imaging increased the reader's confidence category for local and nodal restaging (both p < 0.0001), and the interobserver agreement in identifying nodal recurrences (from moderate to substantial, p < 0.01). However, it significantly increased diagnostic accuracy exclusively for local uptakes rated by low-experienced readers (from 76.5 to 84%, p = 0.05) and for nodal uptakes rated as uncertain at standard imaging (from 68.1 to 78.5%, p < 0.05). In this framework, SUVmax kinetics resulted in an independent predictor of PCa recurrence compared to standard metrics, potentially guiding the dual-phase PET/CT interpretation.
CONCLUSIONS
The present results do not support the systematic combination of forced diuresis and late-phase imaging in the clinical setting, but allow the identification of patients-, lesions-, and reader-based scenarios that might benefit from it.
KEY POINTS
• Increased detection of prostate cancer recurrences has been reported by adding diuretics administration or an additional late abdominopelvic scan to the standard [Ga]Ga-PSMA-11 PET/CT procedure. • We verified the added value of combined forced diuresis and delayed imaging, showing that this protocol only slightly increases the diagnostic accuracy of [Ga]Ga-PSMA-11 PET/CT, thus not justifying its systematic use in clinics. • However, it can be helpful in specific clinical scenarios, e.g., when PET/CT is reported by low-experienced readers. Moreover, it increased the reader's confidence and the agreement among observers.
Topics: Male; Humans; Gallium Radioisotopes; Positron Emission Tomography Computed Tomography; Neoplasm Recurrence, Local; Prostatic Neoplasms; Diuresis; Diuretics; Edetic Acid
PubMed: 36892650
DOI: 10.1007/s00330-023-09516-0 -
European Heart Journal Oct 2019
Topics: Acute Kidney Injury; Diuresis; Humans; Kidney; Transcatheter Aortic Valve Replacement
PubMed: 31263876
DOI: 10.1093/eurheartj/ehz462 -
Therapeutic Advances in Cardiovascular... Oct 2017Chronic congestive heart failure (CHF) is a complex disorder characterized by inability of the heart to keep up the demands on it, followed by the progressive pump... (Review)
Review
Chronic congestive heart failure (CHF) is a complex disorder characterized by inability of the heart to keep up the demands on it, followed by the progressive pump failure and fluid accumulation. Although the loop diuretics are widely used in heart failure (HF) patients, both pharmacodynamic and pharmacokinetic alterations are thought to be responsible for diuretic resistance in these patients. Strategies to overcome diuretic resistance include sodium intake restriction, changes in diuretic dose and route of administration and sequential nephron diuretic therapy. In this review, we discuss the definition, prevalence, mechanism of development and management strategies of diuretic resistance in HF patients.
Topics: Chronic Disease; Diuresis; Drug Resistance; Heart Failure; Hemodynamics; Humans; Kidney; Risk Factors; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 28728476
DOI: 10.1177/1753944717718717 -
Journal of the American Heart... Mar 2022Background Oral NaCl produces a greater natriuresis and diuresis than the intravenous infusion of the same amount of NaCl, indicating the existence of a gastro-renal...
Background Oral NaCl produces a greater natriuresis and diuresis than the intravenous infusion of the same amount of NaCl, indicating the existence of a gastro-renal axis. As one of the major natriuretic hormones secreted by both the intestines and the kidney, we hypothesized that renal uroguanylin interacts with dopamine receptors to increase sodium excretion synergistically, an impaired interaction of which may be involved in the pathogenesis of hypertension. Methods and Results In Wistar-Kyoto rats, the infusion of uroguanylin or fenoldopam (a D-like receptor agonist) induced natriuresis and diuresis. Although subthreshold dosages of uroguanylin or fenoldopam had no effect, the coinfusion of subthreshold dosages of those reagents significantly increased sodium excretion. The coinfusion of an antagonist against D-like receptors, SCH23390, or an antagonist against uroguanylin, 2-methylthioadenosine triphosphate, prevented the fenoldopam- or uroguanylin-mediated natriuresis and diuresis in Wistar-Kyoto rats. However, the natriuretic effects of uroguanylin and fenoldopam were not observed in spontaneously hypertensive rats. The uroguanylin/D-like receptor interaction was also confirmed in renal proximal tubule cells. In renal proximal tubule cells from Wistar-Kyoto rats but not spontaneously hypertensive rats, stimulation of either D-like receptors or uroguanylin inhibited Na-K-ATPase activity, an effect that was blocked in the presence of SCH23390 or 2-methylthioadenosine triphosphate. In renal proximal tubule cells from Wistar-Kyoto rats, guanylyl cyclase C receptor (uroguanylin receptor) and D receptor coimmunoprecipitated, which was increased after stimulation by either uroguanylin or fenoldopam; stimulation of one receptor increased renal proximal tubule cell membrane expression of the other. Conclusions These data suggest that there is synergism between uroguanylin and D-like receptors to increase sodium excretion. An aberrant interaction between the renal uroguanylin and D-like receptors may play a role in the pathogenesis of hypertension.
Topics: Animals; Fenoldopam; Hypertension; Kidney; Kidney Tubules, Proximal; Natriuresis; Natriuretic Peptides; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Dopamine D1; Sodium; Sodium Chloride
PubMed: 35229618
DOI: 10.1161/JAHA.121.022827