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Journal of the American Society of... Jul 2017LCZ-696, sacubitril/valsartan, is a dual-acting molecule consisting of the angiotensin II (Ang II) receptor blocker valsartan and the neprilysin (neutral endopeptidase)... (Review)
Review
LCZ-696, sacubitril/valsartan, is a dual-acting molecule consisting of the angiotensin II (Ang II) receptor blocker valsartan and the neprilysin (neutral endopeptidase) inhibitor AHU-377 with significant beneficial effects in patients with hypertension and heart failure (HF). Several recent studies have demonstrated a higher effectiveness of LCZ-696 compared to valsartan in the treatment of hypertension and HF. The rationale for the development and the Food and Drug Administration approval of LCZ-696 was based on the concept of an additive effect of the Ang II receptor blocker valsartan and the neutral endopeptidase (neprilysin) inhibitor AHU-377 for the treatment of hypertension and HF. The synergism from these drugs arises from the vasodilating effects of valsartan through its blockade of Ang II type 1 receptor and the action of natriuretic peptides atrial natriuretic peptide and B-type natriuretic peptide (BNP) by preventing their catabolism with neprilysin resulting in increase of cyclic guanosine monophosphate. This action of neprilysin is associated with increased natriuresis, diuresis, and systemic vasodilation, since these peptides have been shown to have potent diuretic, natriuretic, and vasodilating effects. In addition, it reduces the levels of N terminal pro-BNP. Therefore, administration of LCZ-696 results in significant reduction of wall stress from pressure and volume overload of the left ventricle as demonstrated by the reduction of N terminal pro-BNP, both significant constituents of hypertension and HF, and it is safe, well tolerated and is almost free of cough and angioedema.
Topics: Aminobutyrates; Angioedema; Angiotensin Receptor Antagonists; Antihypertensive Agents; Atrial Natriuretic Factor; Biphenyl Compounds; Clinical Trials as Topic; Cough; Cyclic GMP; Diuresis; Drug Combinations; Heart Failure; Heart Ventricles; Humans; Hypertension; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Renin-Angiotensin System; Stroke Volume; Tetrazoles; Valsartan; Vasodilation
PubMed: 28652105
DOI: 10.1016/j.jash.2017.04.012 -
Hypertension (Dallas, Tex. : 1979) May 2023The endogenous purine 8-aminoguanine induces diuresis/natriuresis/glucosuria by inhibiting PNPase (purine nucleoside phosphorylase); however, mechanistic details are...
BACKGROUND
The endogenous purine 8-aminoguanine induces diuresis/natriuresis/glucosuria by inhibiting PNPase (purine nucleoside phosphorylase); however, mechanistic details are unknown.
METHODS
Here, we further explored in rats 8-aminoguanine's effects on renal excretory function by combining studies using intravenous 8-aminoguanine, intrarenal artery infusions of PNPase substrates (inosine and guanosine), renal microdialysis, mass spectrometry, selective adenosine receptor ligands, adenosine receptor knockout rats, laser doppler blood flow analysis, cultured renal microvascular smooth muscle cells, HEK293 cells expressing A receptors and homogeneous time resolved fluorescence assay for adenylyl cyclase activity.
RESULTS
Intravenous 8-aminoguanine caused diuresis/natriuresis/glucosuria and increased renal microdialysate levels of inosine and guanosine. Intrarenal inosine, but not guanosine, exerted diuretic/natriuretic/glucosuric effects. In 8-aminoguanine-pretreated rats, intrarenal inosine did not induce additional diuresis/natriuresis/glucosuria. 8-Aminoguanine did not induce diuresis/natriuresis/glucosuria in A-receptor knockout rats, yet did so in A- and A-receptor knockout rats. Inosine's effects on renal excretory function were abolished in A knockout rats. Intrarenal BAY 60-6583 (A agonist) induced diuresis/natriuresis/glucosuria and increased medullary blood flow. 8-Aminoguanine increased medullary blood flow, a response blocked by pharmacological inhibition of A, but not A, receptors. In HEK293 cells expressing A receptors, inosine activated adenylyl cyclase, and this was abolished by MRS 1754 (A antagonist). In renal microvascular smooth muscle cells, 8-aminoguanine and forodesine (PNPase inhibitor) increased inosine and 3',5'-cAMP; however, in cells from A knockout rats, 8-aminoguanine and forodesine did not augment 3',5'-cAMP yet increased inosine.
CONCLUSIONS
8-Aminoguanine induces diuresis/natriuresis/glucosuria by increasing renal interstitial levels of inosine which, via A receptor activation, increases renal excretory function, perhaps in part by increasing medullary blood flow.
Topics: Rats; Humans; Animals; Adenylyl Cyclases; HEK293 Cells; Diuresis; Diuretics; Natriuresis; Receptors, Purinergic P1; Inosine
PubMed: 36802842
DOI: 10.1161/HYPERTENSIONAHA.122.20760 -
International Urogynecology Journal May 2021Nocturia, defined as the act of waking to pass urine during sleeping, is a common problem in older women and is associated with significant morbidity and impairments in... (Review)
Review
INTRODUCTION AND HYPOTHESIS
Nocturia, defined as the act of waking to pass urine during sleeping, is a common problem in older women and is associated with significant morbidity and impairments in health-related quality of life. The aim of this review was to synthesize the current evidence regarding the incidence, impact, pathophysiology, and specific diagnostic approach of nocturia in the postmenopausal population.
METHODS
We searched PubMed and Web of Science databases to identify relevant studies published through June 2020. Reference lists of the reviews obtained were screened for other articles deemed pertinent by the authors.
RESULTS
Genitourinary symptoms attributed to the menopause have been reported to occur in nearly 90% of postmenopausal women, and nocturia is one of the most common. The relative deficiency in endogenous estrogen production after the menopause is thought to exacerbate all major pathophysiological mechanisms that may underlie nocturia, including reduced bladder capacity, nocturnal polyuria, global polyuria, and sleep disorders. Diminished estrogen may induce anatomical and physiological bladder changes, contributing to a reduction in functional bladder capacity. Excess nocturnal urine production can also be provoked by estrogen depletion, either via free water-predominant diuresis by an impaired secretion of antidiuretic hormone, or a salt-predominant diuresis owing to diminished activation of the renin-angiotensin-aldosterone axis. Additionally, a relationship between the transition to menopause and impaired sleep has been described, mediated by increased incidence in vasomotor symptoms and obstructive sleep apnea signs during the menopause.
CONCLUSION
Further research is necessary to better characterize and manage nocturia in postmenopausal women.
Topics: Aged; Diuresis; Female; Humans; Menopause; Nocturia; Polyuria; Quality of Life
PubMed: 33439278
DOI: 10.1007/s00192-020-04640-7 -
Hormonal regulation and functional role of the "renal" tubules in the disease vector, Aedes aegypti.Vitamins and Hormones 2021The Aedes aegypti mosquito is a vector responsible for transmitting various arboviruses including dengue and yellow fever. Their ability to regulate the ionic and water... (Review)
Review
The Aedes aegypti mosquito is a vector responsible for transmitting various arboviruses including dengue and yellow fever. Their ability to regulate the ionic and water composition of their hemolymph is a major physiological phenomenon, allowing the mosquito to adapt to a range of ecological niches. Hematophagus insects, including the female A. aegypti, face the challenge of excess salt and water intake after a blood meal. Post-prandial diuresis is under rigorous control by neuroendocrine factors, acting on the Malpighian "renal" tubules (MTs), to regulate primary urine production. The MTs are made up of two cell types; mitochondria-rich principal cells, which facilitate active transport of Na and K cations across the membrane, and thin stellate cells, which allows for transepithelial Cl secretion. The active driving force responsible for ion transport is the apical V-type H ATPase, which creates a proton gradient allowing for Na and/or K cation exchange through cation/H antiporters. Additionally, the basolaterally localized Na-K-2Cl cotransporter (NKCC) is responsible for the transport of these ions from the hemolymph into the principal cells. Numerous studies have examined hormonal regulation of the mosquito MTs and identified several diuretics including serotonin (5HT), a calcitonin-related diuretic hormone 31 (DH), a corticotropin-related factor like diuretic peptide (DH), a kinin-related diuretic peptide, as well as anti-diuretic factors including CAPA peptides, all of which are known to regulate fluid and ion transport by the MTs. This review therefore focuses on the control of ionic homeostasis in A. aegypti mosquitoes, emphasizing the importance of the MTs, the channels and transporters involved in maintaining hydromineral balance, and the neuroendocrine regulation of both diuresis and anti-diuresis.
Topics: Aedes; Animals; Disease Vectors; Diuresis; Female; Malpighian Tubules; Mosquito Vectors
PubMed: 34420581
DOI: 10.1016/bs.vh.2021.06.007 -
Canadian Family Physician Medecin de... Feb 2015To educate primary health care professionals about the diagnosis and treatment of postobstructive diuresis (POD), a rare but potentially lethal complication associated... (Review)
Review
OBJECTIVE
To educate primary health care professionals about the diagnosis and treatment of postobstructive diuresis (POD), a rare but potentially lethal complication associated with the relief of urinary obstructions.
SOURCES OF INFORMATION
The main concepts and clinical evidence reviewed in this article were derived from a literature search of PubMed and Google Scholar. Expert opinion was used to supplement recommendations in areas with little evidence.
MAIN MESSAGE
Urinary retention is a frequently encountered presentation seen by all physicians. Most family physicians are comfortable treating these patients, initiating investigations, and organizing appropriate follow-up. This article reviews a rare but potentially lethal complication known as POD. Postobstructive diuresis is a polyuric response initiated by the kidneys after the relief of a substantial bladder outlet obstruction. In severe cases this condition can become pathologic, resulting in dehydration, electrolyte imbalances, and death if not adequately treated. Primary care physicians should be familiar with this potential clinical entity, especially as they are generally the first to encounter and treat these patients.
CONCLUSION
Physicians aware of POD will be able to identify patients at risk and arrange the appropriate monitoring after relieving a urinary obstruction. Early diagnosis and treatment of pathologic POD will prevent mortality.
Topics: Dehydration; Diuresis; Family Practice; Humans; Kidney; Physicians, Primary Care; Polyuria; Urinary Retention; Water-Electrolyte Balance
PubMed: 25821871
DOI: No ID Found -
Journal of Pharmacological and... 2022Metabolic chambers are routinely used for urine collection in rodents. In mice, due to small urination volume, evaporation in the metabolic chambers (≈50%) distorts...
Metabolic chambers are routinely used for urine collection in rodents. In mice, due to small urination volume, evaporation in the metabolic chambers (≈50%) distorts diuresis and urinalysis parameters. We have developed a new technique of bladder catheterization enabling long-term accurate and contamination-free urine collection in awake male and female mice for 30 days or longer. Daily diuresis in catheterized mice was twice higher as compared to metabolic cages. The twofold difference in urine recovery was preserved when the circadian variation of diuresis, the effects of furosemide, desmopressin and water load were estimated using the two techniques. Urine osmolarity, urinalysis, and microbiological parameters evidence higher quality of the catheter-collected urine. Using phenol red, we demonstrate utility of our technique for pharmacokinetic studies. 30 days after the surgery the catheters were patent and had minimal impact on the animals' heath. Bladder catheterization is a useful tool for physiological, pharmacological, and toxicological studies.
Topics: Animals; Diuresis; Female; Male; Mice; Urinary Bladder; Urinary Catheterization; Urine Specimen Collection; Wakefulness
PubMed: 34678429
DOI: 10.1016/j.vascn.2021.107128 -
Cardiovascular Diabetology May 2020Glucagon-like peptide-1 (GLP-1) induces diuresis and natriuresis. Previously we have shown that GLP-1 activates afferent renal nerve to increase efferent renal...
BACKGROUND
Glucagon-like peptide-1 (GLP-1) induces diuresis and natriuresis. Previously we have shown that GLP-1 activates afferent renal nerve to increase efferent renal sympathetic nerve activity that negates the diuresis and natriuresis as a negative feedback mechanism in normal rats. However, renal effects of GLP-1 in heart failure (HF) has not been elucidated. The present study was designed to assess GLP-1-induced diuresis and natriuresis in rats with HF and its interactions with renal nerve activity.
METHODS
HF was induced in rats by coronary artery ligation. The direct recording of afferent renal nerve activity (ARNA) with intrapelvic injection of GLP-1 and total renal sympathetic nerve activity (RSNA) with intravenous infusion of GLP-1 were performed. GLP-1 receptor expression in renal pelvis, densely innervated by afferent renal nerve, was assessed by real-time PCR and western blot analysis. In separate group of rats after coronary artery ligation selective afferent renal denervation (A-RDN) was performed by periaxonal application of capsaicin, then intravenous infusion of GLP-1-induced diuresis and natriuresis were evaluated.
RESULTS
In HF, compared to sham-operated control; (1) response of increase in ARNA to intrapelvic injection of GLP-1 was enhanced (3.7 ± 0.4 vs. 2.0 ± 0.4 µV s), (2) GLP-1 receptor expression was increased in renal pelvis, (3) response of increase in RSNA to intravenous infusion of GLP-1 was enhanced (132 ± 30% vs. 70 ± 16% of the baseline level), and (4) diuretic and natriuretic responses to intravenous infusion of GLP-1 were blunted (urine flow 53.4 ± 4.3 vs. 78.6 ± 4.4 µl/min/gkw, sodium excretion 7.4 ± 0.8 vs. 10.9 ± 1.0 µEq/min/gkw). A-RDN induced significant increases in diuretic and natriuretic responses to GLP-1 in HF (urine flow 96.0 ± 1.9 vs. 53.4 ± 4.3 µl/min/gkw, sodium excretion 13.6 ± 1.4 vs. 7.4 ± 0.8 µEq/min/gkw).
CONCLUSIONS
The excessive activation of neural circuitry involving afferent and efferent renal nerves suppresses diuretic and natriuretic responses to GLP-1 in HF. These pathophysiological responses to GLP-1 might be involved in the interaction between incretin-based medicines and established HF condition. RDN restores diuretic and natriuretic effects of GLP-1 and thus has potential beneficial therapeutic implication for diabetic HF patients.
Topics: Animals; Capsaicin; Disease Models, Animal; Diuresis; Diuretics; Glucagon-Like Peptide 1; Heart Failure; Infusions, Intravenous; Kidney; Male; Natriuresis; Rats, Sprague-Dawley; Sympathectomy, Chemical
PubMed: 32384887
DOI: 10.1186/s12933-020-01029-0 -
International Urology and Nephrology Jul 2018Osmotic diuresis results from urine loss of large amounts of solutes distributed either in total body water or in the extracellular compartment. Replacement solutions... (Review)
Review
Osmotic diuresis results from urine loss of large amounts of solutes distributed either in total body water or in the extracellular compartment. Replacement solutions should reflect the volume and monovalent cation (sodium and potassium) content of the fluid lost. Whereas the volume of the solutions used to replace losses that occurred prior to the diagnosis of osmotic diuresis is guided by the clinical picture, the composition of these solutions is predicated on serum sodium concentration and urinary sodium and potassium concentrations at presentation. Water loss is relatively greater than the loss of sodium plus potassium leading to hypernatremia which is seen routinely when the solute responsible for osmotic diuresis (e.g., urea) is distributed in body water. Solutes distributed in the extracellular compartment (e.g., glucose or mannitol) cause, in addition to osmotic diuresis, fluid transfer from the intracellular into the extracellular compartment with concomitant dilution of serum sodium. Serum sodium concentration corrected to euglycemia should be substituted for actual serum sodium concentration when calculating the composition of the replacement solutions in hyperglycemic patients. While the patient is monitored during treatment, the calculation of the volume and composition of the replacement solutions for losses of water, sodium and potassium from ongoing osmotic diuresis should be based directly on measurements of urine volume and urine sodium and potassium concentrations and not by means of any predictive formulas. Monitoring of clinical status, serum sodium, potassium, glucose, other relevant laboratory values, urine volume, and urine sodium and potassium concentrations during treatment of severe osmotic diuresis is of critical importance.
Topics: Body Water; Diuresis; Electrolytes; Female; Humans; Hypernatremia; Male; Monitoring, Physiologic; Osmolar Concentration; Potassium; Sodium; Treatment Outcome; Water-Electrolyte Imbalance
PubMed: 29511980
DOI: 10.1007/s11255-018-1822-0 -
Urolithiasis Jun 2018With an increased risk of symptomatic events, the complications related to residual fragments are complex and intractable. The management of stone fragments is a... (Review)
Review
With an increased risk of symptomatic events, the complications related to residual fragments are complex and intractable. The management of stone fragments is a challenge to urologists. This review focused on the progress, status, and needs of the newly developed physical therapies to remove fragments and improve the stone-free rate. Physical therapies, including mechanical percussion, diuresis, and inversion therapy, ultrasonic propulsion technology, glue-clot technology, and magnetization technology, will facilitate progress in endoscopic stone fragment retrieval.
Topics: Diuresis; Diuretics; Humans; Kidney Calculi; Lithotripsy; Percussion; Physical Therapy Modalities
PubMed: 28593452
DOI: 10.1007/s00240-017-0988-8 -
Journal of the American Heart... Aug 2020
Natriuresis, Diuresis, and Volume Changes in Diabetics With Heart Failure With Preserved Ejection Fraction: Impact of Sodium-Glucose Cotransporter 2 Inhibitors on Natriuretic Peptides.
Topics: Diabetes Mellitus; Diuresis; Glucose; Heart Failure; Humans; Natriuresis; Natriuretic Peptides; Sodium; Sorbitol; Stroke Volume
PubMed: 32805147
DOI: 10.1161/JAHA.120.017666