-
International Journal of Medical... 2024To examine time-dependent functional and structural changes of the lower urinary tract in streptozotocin-induced diabetic rats with or without low-dose insulin...
To examine time-dependent functional and structural changes of the lower urinary tract in streptozotocin-induced diabetic rats with or without low-dose insulin treatment and explore the pathophysiological characteristics of insulin therapy on lower urinary tract dysfunction (LUTD) caused by diabetes mellitus (DM). Female Sprague-Dawley rats were divided into five groups: normal control (NC) group, 4 weeks insulin-treated DM (4-DI) group, 4 weeks DM (4-DM) group, 8 weeks insulin-treated DM (8-DI) group and 8 weeks DM (8-DM) group. DM was initially induced by i.p. injection of streptozotocin (65 mg/kg), and then the DI groups received subcutaneous implantation of insulin pellets under the mid dorsal skin. Voiding behavior was evaluated in metabolic cages. The function of bladder and urethra were evaluated by simultaneous recordings of the cystometrogram and urethral perfusion pressure (UPP) under urethane anesthesia. The function of bladder and urethra were tested by organ bath techniques. The morphologic changes of the bladder and urethra were investigated using Hematoxylin-Eosin and Masson's staining. Both 4-and 8-weeks diabetic rats have altered micturition patterns, including increased 12-h urine volume, urinary frequency/12 hours and voided volume. urodynamics showed the EUS bursting activity duration is longer in 4-DM group and shorter in 8-DM group compared to NC group. UPP change in 8-DM were significantly lower than NC group. While none of these changes were found between DI and NC groups. Organ bath showed the response to Carbachol and EFS in bladder smooth muscle per tissue weights was decreased significantly in 4- and 8-weeks DM groups compared with insulin-treated DM or NC groups. In contrast, the contraction of urethral muscle and maximum urethral muscle contraction per gram of the tissue to EFS stimulation were significantly increased in 4- and 8-weeks DM groups. The thickness of bladder smooth muscle was time-dependently increased, but the thickness of the urethral muscle had no difference. DM-induced LUTD is characterized by time-dependent functional and structural remodeling in the bladder and urethra, which shows the hypertrophy of the bladder smooth muscle, reduced urethral smooth muscle relaxation and EUS dysfunction. Low-dose insulin can protect against diuresis-induced bladder over-distention, preserve urethral relaxation and protect EUS bursting activity, which would be helpful to study the slow-onset, time-dependent progress of DM-induced LUTD.
Topics: Animals; Female; Rats; Diabetes Mellitus, Experimental; Insulin; Lower Urinary Tract Symptoms; Rats, Sprague-Dawley; Streptozocin; Time Factors; Urethra; Urinary Bladder; Urination
PubMed: 38774757
DOI: 10.7150/ijms.95461 -
Bioscience Reports Jun 2024Endothelin (ET) receptor antagonists are being investigated in combination with sodium-glucose co-transporter-2 inhibitors (SGLT-2i). These drugs primarily inhibit the...
UNLABELLED
Endothelin (ET) receptor antagonists are being investigated in combination with sodium-glucose co-transporter-2 inhibitors (SGLT-2i). These drugs primarily inhibit the SGLT-2 transporter that, in humans, is thought to be mainly restricted to the renal proximal convoluted tubule, resulting in increased glucose excretion favouring improved glycaemic control and diuresis. This action reduces fluid retention with ET receptor antagonists. Studies have suggested SGLT-2 may also be expressed in cardiomyocytes of human heart. To understand the potential of combining the two classes of drugs, our aim was to compare the distribution of ET receptor sub-types in human kidney, with SGLT-2. Secondly, using the same experimental conditions, we determined if SGLT-2 expression could be detected in human heart and whether the transporter co-localised with ET receptors.
METHODS
Immunocytochemistry localised SGLT-2, ETA and ETB receptors in sections of histologically normal kidney, left ventricle from patients undergoing heart transplantation or controls. Primary antisera were visualised using fluorescent microscopy. Image analysis was used to measure intensity compared with background in adjacent control sections.
RESULTS
As expected, SGLT-2 localised to epithelial cells of the proximal convoluted tubules, and co-localised with both ET receptor sub-types. Similarly, ETA receptors predominated in cardiomyocytes; low (compared with kidney but above background) positive staining was also detected for SGLT-2.
DISCUSSION
Whether low levels of SGLT-2 have a (patho)physiological role in cardiomyocytes is not known but results suggest the effect of direct blockade of sodium (and glucose) influx via SGLT-2 inhibition in cardiomyocytes should be explored, with potential for additive effects with ETA antagonists.
Topics: Humans; Kidney; Kidney Tubules, Proximal; Myocardium; Receptor, Endothelin A; Receptor, Endothelin B; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38747277
DOI: 10.1042/BSR20240604 -
Circulation. Heart Failure May 2024
Topics: Humans; Heart Failure; Diuretics; Natriuresis; Acute Disease; Treatment Outcome
PubMed: 38742410
DOI: 10.1161/CIRCHEARTFAILURE.124.011579 -
Circulation. Heart Failure May 2024
Topics: Humans; Diuretics; Heart Failure; Natriuresis; Treatment Outcome
PubMed: 38742406
DOI: 10.1161/CIRCHEARTFAILURE.124.011695 -
Circulation. Heart Failure May 2024
Letter by Shahriar et al Regarding Article, "Protocolized Natriuresis-Guided Decongestion Improves Diuretic Response in Acute Heart Failure: The Multicenter ENACT-HF Study".
Topics: Humans; Heart Failure; Natriuresis; Diuretics; Acute Disease; Treatment Outcome
PubMed: 38742399
DOI: 10.1161/CIRCHEARTFAILURE.124.011703 -
European Journal of Heart Failure Jun 2024
Topics: Humans; Heart Failure; Natriuresis; Acute Disease; Kidney; Glomerular Filtration Rate
PubMed: 38740573
DOI: 10.1002/ejhf.3278 -
Physiological Reports May 2024The pathophysiology behind sodium retention in heart failure with preserved ejection fraction (HFpEF) remains poorly understood. We hypothesized that patients with HFpEF...
The pathophysiology behind sodium retention in heart failure with preserved ejection fraction (HFpEF) remains poorly understood. We hypothesized that patients with HFpEF have impaired natriuresis and diuresis in response to volume expansion and diuretic challenge, which is associated with renal hypo-responsiveness to endogenous natriuretic peptides. Nine HFpEF patients and five controls received saline infusion (0.25 mL/kg/min for 60 min) followed by intravenous furosemide (20 mg or home dose) 2 h after the infusion. Blood and urine samples were collected at baseline, 2 h after saline infusion, and 2 h after furosemide administration; urinary volumes were recorded. The urinary cyclic guanosine monophosphate (ucGMP)/plasma B-type NP (BNP) ratio was calculated as a measure of renal response to endogenous BNP. Wilcoxon rank-sum test was used to compare the groups. Compared to controls, HFpEF patients had reduced urine output (2480 vs.3541 mL; p = 0.028), lower urinary sodium excretion over 2 h after saline infusion (the percentage of infused sodium excreted 12% vs. 47%; p = 0.003), and a lower baseline ucGMP/plasma BNP ratio (0.7 vs. 7.3 (pmol/mL)/(mg/dL)/(pg/mL); p = 0.014). Patients with HFpEF had impaired natriuretic response to intravenous saline and furosemide administration and lower baseline ucGMP/plasma BNP ratios indicating renal hypo-responsiveness to NPs.
Topics: Humans; Heart Failure; Male; Female; Aged; Pilot Projects; Stroke Volume; Furosemide; Sodium; Natriuretic Peptide, Brain; Kidney; Middle Aged; Natriuresis; Diuretics; Cyclic GMP; Aged, 80 and over
PubMed: 38740564
DOI: 10.14814/phy2.16033 -
JACC. Heart Failure Apr 2024Limited evidence exists regarding efficacy and safety of diuretic regimens in ambulatory, congestion-refractory, chronic heart failure (CHF) patients.
BACKGROUND
Limited evidence exists regarding efficacy and safety of diuretic regimens in ambulatory, congestion-refractory, chronic heart failure (CHF) patients.
OBJECTIVE
To compare the potency and safety of commonly used diuretic regimens in CHF patients.
METHODS
A prospective, randomized, open-label, crossover study conducted in NYHA class II-IV CHF patients, treated in an ambulatory day-care unit. Each patient received 3 different diuretic regimens: intravenous (IV) furosemide 250mg; IV furosemide 250mg plus oral metolazone 5mg; and IV furosemide 250mg plus IV acetazolamide 500mg. Treatments were administered once a week, in one of six randomized sequences. The primary endpoint was total sodium excretion, and the secondary was total urinary volume excreted, both measured for 6 hours post-treatment initiation.
RESULTS
A total of 42 patients were recruited. Administration of furosemide plus metolazone resulted in the highest weight of sodium excreted, 4691 mg (95% CI: 4153-5229) compared to furosemide alone 3835 mg (95% CI: 3279-4392), P=0.015 and to furosemide plus acetazolamide 3584 mg (95% CI: 3020-4148), P=0.001. Furosemide plus metolazone resulted in 1.84 liters of urine (95% CI: 1.63-2.05), compared to 1.58 liters (95% CI: 1.37-1.8) P=0.039 collected following administration of furosemide plus acetazolamide and 1.71 liters (95% CI 1.49-1.93) following furosemide alone. The incidence of worsening renal function (WRF) was significantly higher when adding metolazone (41%) to furosemide compared to furosemide alone (17%) and to furosemide plus acetazolamide (2.6%), P<0.001.
CONCLUSIONS
In ambulatory CHF patients, furosemide plus metolazone resulted in a significantly higher natriuresis compared to IV furosemide alone or furosemide plus acetazolamide.
PubMed: 38739124
DOI: 10.1016/j.jchf.2024.04.014