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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 -
Heliyon Dec 2023Forssk. Decne is a member of family Apocynaceae and locally known as 'Khipp'. It is found in dry, sandy habitat of Pakistan and in several other regions around the...
BACKGROUND
Forssk. Decne is a member of family Apocynaceae and locally known as 'Khipp'. It is found in dry, sandy habitat of Pakistan and in several other regions around the world including Asia, Tropical Africa, Western Gulf and Mediterranean countries. It has nutritional value, containing 4 % lipids, 23 % proteins, 28 % carbohydrates, 4 % fibers, vitamin E and several minerals. Traditionally, this plant has been used by several communities for pain, different inflammatory and kidney disorders. Ethno-botanical studies have reported the use of in nephrolithiasis kidney disorders and induction of diuresis, which requires a detailed pharmacological study to validate the folkloric use of as diuretic.
METHODS
The 70 % methanolic (Lp.Cr) extract was prepared and qualitatively checked for the presence of various phytochemicals. Phenolic, flavonoid, tannin and saponin contents were quantified. GC-MS analysis of Lp.Cr was also performed. Antioxidant potential of Lp.Cr was evaluated by DPPH, ABTS and nitrite radical scavenging assays. CUPRAC and FRAP assay described the reducing potential of Lp.Cr. Diuretic activity was performed in both acute and prolonged models at different doses followed by the estimation of electrolytes, urea and creatinine levels. The mechanism of diuresis was described by pre-treatment with atropine, l-NAME, indomethacin and carbonic anhydrase inhibition.
RESULTS
Lp.Cr. indicated high phenolic and flavonoid contents which correlated with good antioxidant activity. GC-MS analysis showed the presence of 104 compounds from different phytochemical classes. Diuretic activity was performed at 10-300 mg/kg concentrations where the dose of 100 and 300 mg/kg showed good diuretic and saluretic activity comparable to furosemide. Lp.Cr exhibited diuresis both in acute and prolonged study protocols which can be attributed to carbonic anhydrase inhibition, effect on prostaglandins and cholinergic pathways.
CONCLUSION
contained several phytochemicals and exhibited good antioxidant activity. It induced diuresis and saluretic activity which was comparable to furosemide at higher doses. Diuretic activity can be attributed to carbonic anhydrase inhibition, prostaglandin synthesis and cholinergic pathways.
PubMed: 38076186
DOI: 10.1016/j.heliyon.2023.e22485 -
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 -
Medicine Mar 2022In allogeneic hematopoietic stem cell transplantation (AHSCT), falls can lead to immediate and late consequences and in some cases to death. We analyzed risks and causes... (Observational Study)
Observational Study
In allogeneic hematopoietic stem cell transplantation (AHSCT), falls can lead to immediate and late consequences and in some cases to death. We analyzed risks and causes of falls with root cause analysis (RCA) based on which improvement interventions were implemented.A retrospective observational study was conducted to analyze with RCA data of incidence reports and medical records of patients admitted; an expert panel identified actions to prevent falls, which were collected in a checklist.Between December 2017 and November 2019, 214 patients were admitted to ordinary hospital stays for AHSCT or AHSCTrelated complications. In this period, 15 falls, involving 11 patients, occurred resulting in a 2.32 d/patient incidence. In 66.67% of cases minor head trauma occurred. Diuretic drugs (93.33%), induced hyper-diuresis in nonbladder catheter patients (93.33%) and antihypertensive drugs (93.33%) were reported as most common cause in our incident reports. The most frequent fall time slot was between 10 PM and 7 AM (60%). We determined with RCA diuretics and consequent induced hyper-diuresis (80%), self-insufficiency (40%), antihypertensive (33.3%) and noncompliance (33.3%) as the most common cause of falls. Finally, 16 actions, collected in a "safe comfort" checklist, were identified to prevent falls.Diuretic drugs inducing hyper-diuresis, self-insufficiency, poor patient compliance, orthostatic hypotension, fever, night-time and obstacles within inpatient units are the most common contributing factors. Therefore, administration of diuretic and antihypertensive drugs should be rescheduled and a multidimensional risk assessment scale integrated with a preventive action plan, such as the safe comfort checklist, should be implemented to reduce falls.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Retrospective Studies; Risk Assessment; Risk Factors; Root Cause Analysis; Stem Cell Transplantation
PubMed: 35356952
DOI: 10.1097/MD.0000000000029132 -
Circulation Research Apr 2023
Topics: Humans; Natriuresis; Cyclic GMP; Hypertension; Sodium; Atrial Natriuretic Factor; Blood Pressure
PubMed: 37104563
DOI: 10.1161/CIRCRESAHA.123.322778 -
Frontiers in Physiology 2022The kidney plays an essential role in homeostasis, accomplished through the regulation of pH, electrolytes and fluids, by the building blocks of the kidney, the...
The kidney plays an essential role in homeostasis, accomplished through the regulation of pH, electrolytes and fluids, by the building blocks of the kidney, the nephrons. One of the important markers of the proper functioning of a kidney is the glomerular filtration rate. Diabetes is characterized by an enlargement of the glomerular and tubular size of the kidney, affecting the afferent and efferent arteriole resistance and hemodynamics, ultimately leading to chronic kidney disease. We postulate that the diabetes-induced changes in kidney may exhibit significant sex differences as the distribution of renal transporters along the nephron may be markedly different between women and men, as recently shown in rodents. The goals of this study are to (i) analyze how kidney function is altered in male and female patients with diabetes, and (ii) assess the renal effects, in women and men, of an anti-hyperglycemic therapy that inhibits the sodium-glucose cotransporter 2 (SGLT2) in the proximal convoluted tubules. To accomplish these goals, we have developed computational models of kidney function, separate for male and female patients with diabetes. The simulation results indicate that diabetes enhances Na transport, especially along the proximal tubules and thick ascending limbs, to similar extents in male and female patients, which can be explained by the diabetes-induced increase in glomerular filtration rate. Additionally, we conducted simulations to study the effects of diabetes and SGLT2 inhibition on solute and water transport along the nephrons. Model simulations also suggest that SGLT2 inhibition raises luminal [Cl] at the macula densa, twice as much in males as in females, and could indicate activation of the tubuloglomerular feedback signal. By inducing osmotic diuresis in the proximal tubules, SGLT2 inhibition reduces paracellular transport, eventually leading to diuresis and natriuresis. Those effects on urinary excretion are blunted in women, in part due to their higher distal transport capacity.
PubMed: 35153824
DOI: 10.3389/fphys.2022.741121 -
Journal of the American College of... Apr 2024Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential.
OBJECTIVES
The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment.
METHODS
DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance.
RESULTS
Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor-naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51-4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d [95% CI: 1.98-3.51]; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L [95% CI: 0.45-10.5]; P < 0.05) and late (7.8 pmol/L [95% CI: 2.77-12.81]; P < 0.01), leading to proportional reductions in free water clearance (early: -9.1 mL/kg/d [95% CI: -14 to -4.12; P < 0.001]; late: -11.0 mL/kg/d [95% CI: -15.94 to -6.07; P < 0.0001]) and elevated urine concentrations (late: 134 mmol/L [95% CI: 39.28-229.12]; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d [95% CI: -1.97 to 7.48; P = 0.25]; mean difference late: 0.9 mL/kg/d [95% CI: -3.83 to 5.62]; P = 0.70).
CONCLUSIONS
Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment [DAPA-Shuttle1]; NCT04080518).
Topics: Aged; Humans; Middle Aged; Benzhydryl Compounds; Conservation of Water Resources; Diuresis; Diuretics, Osmotic; Glucosides; Heart Failure; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Function, Left; Water
PubMed: 38599715
DOI: 10.1016/j.jacc.2024.02.020 -
Frontiers in Endocrinology 2023Within insects, corticotropin-releasing factor/diuretic hormones (CRF/DHs) are responsible for the modulation of a range of physiological and behavioural processes such...
Within insects, corticotropin-releasing factor/diuretic hormones (CRF/DHs) are responsible for the modulation of a range of physiological and behavioural processes such as feeding, diuresis, and reproduction. Rhopr-CRF/DH plays a key role in feeding and diuresis in , a blood-gorging insect and a vector for human Chagas disease. Here, we extend our understanding on the role of this neurohormone in reproduction in adult female . Double-label immunohistochemistry displays co-localized staining of CRF-like and the glycoprotein hormone (GPA2/GPB5) subunit GPB5-like immunoreactivity in the same neurosecretory cells (NSCs) in the mesothoracic ganglionic mass (MTGM) and in their neurohemal sites in adult female , suggesting these peptides could work together to regulate physiological processes. qPCR analysis reveals that the transcript for Rhopr-CRF/DH receptor 2 () is expressed in reproductive tissues and fat body (FB) in adult female , and its expression increases post blood meal (PBM), a stimulus that triggers diuresis and reproduction. Using RNA interference, transcript expression of was knocked down, and egg production monitored by examining the major yolk protein, vitellogenin (Vg), the number and quality of eggs laid, and their hatching ratio. Injection of dsCRFR2 into adult females reduces transcript expression, accelerates oogenesis, increases the number of eggs produced, and reduces hatching rate in female . Downregulation of leads to an increase in the transcript expression of in the fat body and ovaries, and increases the transcript level for the Vg receptor, , in the ovaries. A significant increase in Vg content in the fat body and in the hemolymph is also observed. Incubation of isolated tissues with Rhopr-CRF/DH leads to a significant decrease in transcript expression of in the fat body and in the ovaries. In addition, Rhopr-CRF/DH reduces transcript expression of the ecdysteroid biosynthetic enzymes and reduces ecdysteroid titer in the culture medium containing isolated ovaries. These results suggest the involvement of the CRF-signaling pathway in reproduction, and that Rhopr-CRF/DH acts as a gonad-inhibiting hormone in the adult female , as previously shown for the colocalized glycoprotein, GPA2/GPB5.
Topics: Animals; Female; Adult; Humans; Corticotropin-Releasing Hormone; Diuretics; Rhodnius; Ecdysteroids; Gonadal Hormones; Glycoproteins; Gonads
PubMed: 37842303
DOI: 10.3389/fendo.2023.1279929 -
Drugs in Context 2023Diuresis with loop diuretics is the mainstay treatment for volume optimization in patients with congestive heart failure, in which perfusion and volume expansion play a... (Review)
Review
Diuresis with loop diuretics is the mainstay treatment for volume optimization in patients with congestive heart failure, in which perfusion and volume expansion play a crucial role. There are robust guidelines with extensive evidence for the management of heart failure; however, clear guidance is needed for patients who do not respond to standard diuretic treatment. Diuretic resistance (DR) can be defined as an insufficient quantity of natriuresis with proper diuretic therapy. A combination of diuretic regimens is used to overcome DR and, more recently, SGLT2 inhibitors have been shown to improve diuresis. Despite DR being relatively common, it is challenging to treat and there remains a notable lack of substantial data guiding its management. Moreover, DR has been linked with poor prognosis. This review aims to expose the multiple approaches for treatment of patients with DR and the importance of intravascular volume expansion in the response to therapy.
PubMed: 38188263
DOI: 10.7573/dic.2023-6-5 -
Clinical and Experimental Hypertension... Dec 2024Physical activity has profound benefits on health, especially in patients with cardiovascular and metabolic disease. Exercise training can reduce oxidative stress,...
BACKGROUND
Physical activity has profound benefits on health, especially in patients with cardiovascular and metabolic disease. Exercise training can reduce oxidative stress, improve renal function, and thus lower blood pressure. However, the effect of exercise training on angiotensin II type 1 receptors (ATR) and endothelin subtype B receptors (ETBR)-mediated diuresis and natriuresis in obese Zucker rats is unclear.
METHODS
Lean and obese Zucker rats were exercised or placed on a nonmoving treadmill for 8 weeks. Blood pressure was measured by tail-cuff plethysmography, and functions of ATR and ETBR in the kidney were measured by natriuresis, respectively.
RESULTS
Our data showed that exercise training improved glucose and lipid metabolism, renal function and sodium excretion in obese Zucker rats, accompanied by decreased oxidative stress and GRK4 expression in obese Zucker rats. Moreover, exercise training reduced the Candesartan-induced an increase in diuresis and natriuresis and increased ETBR agonists (BQ3020)-mediated diuresis and natriuresis in obese Zucker rats, which were associated with decreased renal ATR expression and ETBR phosphorylation levels.
CONCLUSIONS
The results demonstrate that exercise training lowers blood pressure via improving renal ATR and ETBR function through modulating GRK4 expression in Obese Zucker Rats and provides potentially effective targets for obesity-related hypertension.
Topics: Humans; Rats; Animals; Rats, Zucker; Kidney; Hypertension; Obesity; Blood Pressure; G-Protein-Coupled Receptor Kinase 4
PubMed: 38471134
DOI: 10.1080/10641963.2024.2323532