Significant Increase In Natriuresis Research Articles

Changes of natriuresis and prediction of cardiovascular events in patients with type 2 diabetes and decompensated heart failure over therapy with sodium-glucose cotransporter 2 inhibitors and standard diuretic therapy

Aim. To evaluate the influence and changes of clinical and water-electrolyte parameters on the risk of cardiovascular events in the early period after decompensated heart failure (HF) in patients with type 2 diabetes (T2D), taking into account the influence of standard diuretic therapy and diuretic therapy in combination with sodium-glucose cotransporter 2 (SGLT-2) inhibitors.Material and methods. The study included 119 patients with type 2 diabetes and class III-IV HF. The duration of diagnosed HF at the time of enrollment was 6,9±1,1 years.Patients who met the inclusion criteria at the time of hospital admission were randomized into a group of standard therapy for decompensated HF (control group) and a group of combined diuretic therapy — loop diuretics + SGLT-2 inhibitors (main group).Results. Against the background of combined diuretic therapy with SGLT-2 inhibitors, a significant increase in diuresis was achieved, starting from the 2nd day: on day 2 — in the main group 1,342,83±159,74 ml/day and 1,250,17±134,53 ml/day in the control group (p=0,001, 95% confidence interval (CI)), on day 3, in the main — 1,895,17±249,95 ml/day, and in the control — 1,723,78±252,49 ml/day (p=0,004, 95% CI), on day 4, in the main — 2,382,50±246,29 ml/day and in the control — 2,124,83±2,86,44 ml/day (p=0,000002, 95% CI), on day 5, in the main — 2,785,50±282,38 ml/day and in the control group 2,458,39±273,36 ml/day (p<0,001, 95% CI).A comparison of the two groups showed a significant increase in natriuresis in the main group on day 5 (+111,1±10,54 ml) compared to the control (+75,53±15,01 ml, p<0,001, 95% CI). Extracellular fluid volume, determined by bioelectrical impedance analysis on day 5, decreased significantly higher when taking SGLT-2 inhibitors: in the main group the decrease was by 5,48±2,19 kg, in the control group — by 2,92±0,73 kg (p=0,02, 95% CI), On day 5, we revealed a significant inverse relationship between natriuresis level and extracellular fluid volume (r=0,217, p=0,018). Dapagliflozin (D), like empagliflozin (E), significantly and equally increases the level of natriuresis (D +108,25±13,56 mmol/day, p<0,001, E +112,52±8,50, p=0,00009) and reduces the extracellular fluid volume (D -5,05±1,46 kg, p<0,001, E -5,69±2,47, p<0,001) on day 5.Conclusion. In patients with type 2 diabetes hospitalized for decompensated HF, therapy with SGLT-2 inhibitors + loop diuretics lead to a significantly greater diuresis, natriuresis and a greater decrease in extracellular fluid volume. A significant inverse relationship was found between the extracellular fluid volume and natriuresis level on day 5. Dapagliflozin effectiveness in edema, assessed by natriuresis level on day of treatment, is identical to the empagliflozin.

Effects of Sacubitril/Valsartan (LCZ696) on Natriuresis, Diuresis, Blood Pressures, and NT-proBNP in Salt-Sensitive Hypertension.

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01681576.

Role of Vasopressin in the Regulation of Renal Sodium Excretion: Interaction with Glucagon‐Like Peptide‐1

The present study aimed to investigate the potential physiological role of vasopressin and the incretin hormone of the gastrointestinal tract (glucagon-like peptide-1; GLP-1) in the regulation of the water-salt balance in a hyperosmolar state as a result of sodium loadings. In rats, the administration of hypertonic NaCl solution resulted in a significant increase in natriuresis, which correlated with the vasopressin excretion rate. Natriuresis following an i.p. NaCl load (23.2±1.4μmol/min/kg) was enhanced by inhibition of V2 receptors (51.6±3.7μmol/min/kg, P<0.05) and was reduced by a V1a antagonist injection (6.3±1.1μmol/min/kg, P<0.05). Compared to i.p. salt administration, oral NaCl loading induced a significant increase in the plasma GLP-1 level within 5min and resulted in more prominent natriuresis and a smaller increase in blood sodium concentration. It was hypothesised that the basis for the fast elimination of excess sodium following an oral NaCl load could be the involvement of GLP-1 in osmoregulation combined with vasopressin. It was demonstrated that GLP-1 mimetic exenatide (1.5nmol/kg) produced a significant decrease in proximal reabsorption and an increase in fractional sodium excretion (from 0.15±0.04% to 9±1%). It was also shown that vasopressin at doses of 1-10μg/kg and the selective V1a agonist (1μg/kg) induced an increase in sodium fractional excretion to 10±2% and 8±2%, respectively. Combined administration of exenatide and V1a agonist revealed their cumulative natriuretic effect, and sodium fractional excretion increased by up to 18±2%. These data suggest that GLP-1 combined with vasopressin could be involved in the regulation of sodium balance in the hyperosmolar state as a result of NaCl loading. Vasopressin regulates the reabsorption of a significant portion of filtered sodium in the distal segment of the nephron and modulates the natriuretic effect of GLP-1.

Biological effect of Opuntia ficus indica (L.) Mill. (Cactaceae) waste matter : Note I: diuretic activity

In this work we studied in rat the diuretic activity of Opuntia ficus indica (L.) Mill. (Cactaceae) waste matter. The cladodes, flowers and non commerciable fruits were collected in S. Cono (CT, Sicily) cultivation. Acute and chronic diuretic activity of 15% infusion of cladodes, flowers and fruits were assayed. Natriuresis, kaliuresis and the activity on fructose-induced hyperuricemia was also studied. The results show that O. ficus indica cladode, fruit and flower infusions significantly increase diuresis. This effect is more marked with the fruit infusion and it is particularly significant during the chronic treatment. The fruit infusion shows also antiuric effect. In all experiments cladode, flower and fruit infusions showed a modest but not significant increase in natriuresis and kaliuresis.

Natriuretic and diuretic effects of felodipine and hydrochlorothiazide after single and repeated doses

The effects of the calcium antagonist, felodipine, and hydrochlorothiazide (HCTZ) on natriuresis/diuresis and blood pressure were evaluated in 12 healthy subjects. The investigation was designed as a double-blind, three-way, randomised, crossover study, and all comparisons were performed against placebo. Urine volume, urine sodium excretion, heart rate and blood pressure were measured after a single dose of felodipine 10 mg, HCTZ 12.5 mg or placebo as well as during steady-state conditions (6 days of treatment with felodipine 10 mg b.i.d., HCTZ 12.5 mg b.i.d. or placebo). A significant increase in natriuresis was seen in the first 4 h after a single dose of felodipine and HCTZ, and the effect of felodipine was approximately 40% that of HCTZ. When the entire 24-h period after a single dose was studied, there was a significant increase in natriuresis after HCTZ, but not after felodipine, compared with placebo. A significant increase in diuresis was found in the first 4 h after a single dose of HCTZ, but not after felodipine, compared with placebo. Under steady-state conditions, there were no statistically significant differences between felodipine and placebo or HCTZ and placebo when the 24-h period, as a whole was considered. Potassium excretion was not affected by any of the drugs. Felodipine caused a significant decrease in diastolic blood pressure in this study. This was not the case for HCTZ or placebo.

Contribution of the baroreflex afferent nerves to the production of vasoconstricted hypertension in volume-expanded dogs.

Dextran in lactated Ringer's solution (20 ml/kg) was infused for 1 hour into anesthetized dogs with sinoaortic denervation and vagotomy (deafferentation; n = 10) and dogs treated with hexamethonium (de-efferentation; n = 13) to compare with our previous observation in dogs with an intact autonomic nervous system (control, n = 34). During the infusion, increase in blood pressure associated with increase in cardiac output was observed in all three groups. The increases in blood pressure were larger in the two groups with an impaired autonomic nervous system. In the recovery period, the control dogs and the hexamethonium-treated dogs showed gradual increases in total peripheral resistance and in vasoconstricted hypertension 3 hours after stopping the infusion. In contrast, the dogs with sinoaortic denervation and vagotomy did not show any increase in total peripheral resistance. The vasoconstricted groups showed peaks of natriuresis soon after the infusion, not 3 hours after the infusion when vasoconstriction was observed, although the dogs with deafferentation did not show a significant increase in natriuresis. Norepinephrine (0.5 micrograms/kg) was administered intravenously before and after volume expansion, and the pressor responses in the three groups after volume expansion were enhanced similarly (143%, 128%, and 136%, respectively). These results indicate that the afferent signals from peripheral vessels to the brain contribute to the production of vasoconstricted hypertension after acute volume expansion and that the vasoconstriction is independent of pressor hypersensitivity and is dissociated in time from the natriuresis.