Low-dose Atrial Natriuretic Peptide Research Articles

Effect of low-dose atrial natriuretic peptide in critically ill patients with acute kidney injury: a retrospective, single-center study with propensity-score matching

BackgroundAcute kidney injury (AKI) is a major comorbidity in critically ill patients. Low-dose atrial natriuretic peptide (ANP) has been shown to effectively prevent acute kidney injury (AKI), especially in cardiovascular surgery patients. However, its treatment effects for AKI in critically ill patients are unclear.MethodsThis single-center, retrospective, observational study included patients with AKI diagnosed within 7 days after intensive care unit (ICU) admission during the period January 2010 to December 2017. We conducted a propensity-matched analysis to estimate the treatment effect of low-dose carperitide (a recombinant human ANP) on the clinical outcomes. The primary outcome was a composite of death, renal replacement therapy dependence, or no recovery from AKI (defined as an increase of the serum creatinine level to ≥200% of baseline) at hospital discharge.ResultsDuring the study period, 4479 adult patients were admitted to the ICU. We identified 1374 eligible patients with AKI diagnosed within 7 days after ICU admission. Among these patients, 346 (25.2%) were treated with low-dose carperitide, with an average dose of 0.019 μg kg− 1 min− 1. The primary outcome occurred more often in the treatment group than in the control group (29.7% versus 23.4%, respectively; p = 0.022). After propensity score matching, characteristics of 314 patients from each group were well- balanced. Significant difference of the primary outcome, as seen with the full cohort, was no longer obtained; no benefit of carperitide was detected in the matched cohort (29.0% versus 25.2%; p = 0.281).ConclusionsLow-dose ANP showed no treatment effect in general critically ill patients who developed AKI.

Low-dose atrial natriuretic peptide for prevention or treatment of acute kidney injury: a systematic review and\xa0meta-analysis

BackgroundTheoretically, atrial natriuretic peptide (ANP), especially low-dose ANP, is beneficial in acute kidney injury (AKI). In this study, we examined whether low-dose ANP is effective in preventing or treating AKI by conducting an updated systematic review for randomized controlled trials (RCTs).MethodWe searched the Excerpta Medica database (EMBASE), PubMed, and Cochrane CENTRAL databases for RCTs that compare the effects of low-dose ANP (≤ 50 ng/kg/min) with a placebo or conventional therapy in at-risk patients or patients with AKI. The primary outcome was the incidence of new AKI (in prevention RCTs), while the secondary outcomes were in-hospital mortality rate, renal replacement therapy (RRT) requirement, length of hospital and intensive care unit (ICU) stay, incidence of hypotension, and peak serum creatinine levels. The risk-of-bias was evaluated using the Cochrane Collaboration risk-of-bias tool. Trial sequential analysis (TSA) was used for each outcome of interest.ResultsA total of 18 RCTs (16 prevention and two treatment trials) fulfilled our inclusion criteria. In prevention RCTs, the incidence of new AKI was significantly low in the low-dose ANP group (relative risk [RR] = 0.51; 95% confidence interval [CI] = 0.36–0.72; P = 0.0001) compared to the control group. In addition, the low-dose ANP group showed a significantly reduced RRT requirement in both prevention (RR = 0.17; 95% CI = 0.04–0.64; P = 0.009) and treatment (RR = 0.43; 95% CI = 0.20–0.93; P = 0.03) RCTs. Among secondary outcomes, in some cases, low-dose ANP was associated with a reduction in ICU and in-hospital stay. The risk-of-bias assessment and TSA results indicated that the sample sizes and qualities of the RCTs were insufficient to conclude the efficacy of low-dose ANP.ConclusionLow-dose ANP might be effective in preventing or treating AKI. However, the evidence accumulated so far is not strong enough to demonstrate ANP’s beneficial effects. The next step is to elucidate the effects of low-dose ANP by conducting multicenter, high-quality, large-sample RCTs.Trial registrationPROSPERO registry CRD42017068568. Registered 20 June 2017.

Molecular mechanisms underlying the neuroprotective role of atrial natriuretic peptide in experimental acute ischemic stroke.

Molecular mechanisms underlying the neuroprotective role of atrial natriuretic peptide in experimental acute ischemic stroke.

Role of atrial natriuretic peptide in controlling diabetic nephropathy in rats.

Abstract Background Diabetes is a downregulator of atrial natriuretic peptide (ANP), resulting in reduced nitric oxide level and low expression of endothelial nitric oxide synthase by which nitric oxide level get reduced. In the present study, we examined the role of ANP in reduced nitric oxide level, which may be responsible in controlling diabetic nephropathy in rats. Methods Serum nitrite/nitrate ratio, blood urea nitrogen, protein in urine, urinary output, serum creatinine, serum cholesterol, kidney weight, kidney hypertrophy, renal cortical collagen content, thiobarbituric acid level, and antioxidant enzymatic activities were assessed. Results Treatment with lisinopril (1 mg/kg) significantly attenuated diabetes-induced elevated glucose level, cholesterol level, and protein in urine concentration. Whereas ANP at low dose (5 μg/kg) has no effect on elevated markers of diabetic nephropathy, treatment with intermediate (10 μg/kg) and high-dose ANP (20 μg/kg) significantly attenuated the diabetes-induced increased blood urea nitrogen, protein in urine, urinary output, creatinine, cholesterol, kidney weight, kidney hypertrophy, renal collagen content, and thiobarbituric acid level and reduced endogenous antioxidant enzymatic activities. High dose of ANP was more effective in attenuating the diabetes-induced nephropathy, renal oxidative stress, and antioxidant enzyme activity as compared with the treatment with low-dose ANP (5 μg/kg), intermediate-dose ANP (10 μg/kg), or lisinopril (1 mg/kg, employed as standard agent). Administration of erythro-9-(2-hydroxy-3-nonyl)adenine, a phosphodiesterase-2 inhibitor (3 mg/kg), in combination with high-dose ANP significantly attenuated high-dose ANP induced ameliorative effects in diabetic nephropathy. Conclusions Taken together, these results indicate that diabetes-induced oxidative stress and lipid alterations may be responsible for the induction of nephropathy in diabetic rats. ANP at intermediate and high doses have prevented the development of diabetes-induced nephropathy by reducing the cholesterol level, protein in urine concentration, and renal oxidative stress and by increasing the nitrite/nitrate ratio, certainly providing the direct nephroprotective action.

Effects of low-dose atrial natriuretic peptide infusion on cardiac surgery–associated acute kidney injury: A multicenter randomized controlled trial

Effects of low-dose atrial natriuretic peptide infusion on cardiac surgery–associated acute kidney injury: A multicenter randomized controlled trial

36th International Symposium on Intensive Care and Emergency Medicine : Brussels, Belgium. 15-18 March 2016.

36th International Symposium on Intensive Care and Emergency Medicine : Brussels, Belgium. 15-18 March 2016.

Reduction in the incidence of acute kidney injury after aortic arch surgery with low-dose atrial natriuretic peptide

Acute kidney injury (AKI) after surgery is associated with an increased risk of adverse events and death. Atrial natriuretic peptide (ANP) dilates the preglomerular renal arteries and inhibits the renin-angiotensin axis. A low-dose ANP infusion increases glomerular filtration rate after cardiovascular surgery, but it is not known whether it reduces the incidence of AKI or the mortality rate. To evaluate whether an intravenous ANP infusion prevents AKI in patients undergoing aortic arch surgery requiring hypothermic circulatory arrest. A randomised controlled study. Operating room and intensive care unit at Kawasaki Saiwai Hospital, Kanagawa, Japan. Forty-two patients with normal preoperative renal function undergoing elective repair of an aortic arch aneurysm. Patients were assigned randomly to receive a fixed dose of ANP (0.0125 μg (-1) kg(-1) min) or placebo. The infusion was started after induction of anaesthesia and continued for 24 h postoperatively. The primary end-point was the incidence of AKI within 48 h after surgery. AKI developed in 30% of patients who received ANP compared with 73% of patients who received placebo (P = 0.014). Intraoperative urine output was almost 1 l greater in patients who received ANP (1865 ± 1299 versus 991 ± 480 ml in the control group, P = 0.005). However, there were no differences in mean arterial pressure or number of episodes of hypotension between the groups. Length of hospital and intensive care stays were not significantly different, nor was there a difference in 30-day mortality. No patients required haemodialysis or continuous renal replacement therapy. We found that an intravenous infusion of ANP at 0.0125 μg kg(-1) min(-1) is an effective intervention for reducing the incidence of postoperative AKI, and appears to afford a degree of renal protection during and after cardiovascular surgery. Kawasaki ANP trial, UMIN Clinical Trials Registry ID: UMIN000011650.

Low-dose B-type natriuretic peptide raises cardiac sympathetic nerve activity in sheep

The reported effects of atrial natriuretic peptide (ANP) on sympathetic nerve activity (SNA) are variable, dependent on concomitant hemodynamic actions, and likely to be regionally differentiated. There are few reports of the effect of B-type natriuretic peptide (BNP) on SNA and none have measured cardiac SNA (CSNA) by direct microneurography. We measured the effects of low-dose ANP and BNP (2.4 pmol·kg(-1)·min(-1) infused for 120 min) on CSNA and hemodynamics in conscious sheep (n = 8). While there was a trend for mean arterial pressure and cardiac output to fall with both ANP and BNP, changes were not significant compared with vehicle control. However, BNP did significantly reduce systolic arterial (97 ± 4.2 vs. 107 ± 6.8 mmHg during control; P = 0.043) and pulse pressures (0.047) and increase heart rate (110 ± 6.7 vs. 96 ± 7.3 beats/min; P = 0.044). Trends for these hemodynamic parameters to change with ANP did not achieve statistical significance. ANP also had no significant effect on any CSNA parameters measured. In contrast, BNP induced a rise in both CSNA burst frequency (∼20 bursts/min higher than control, P = 0.011) and burst area (∼40% higher than control, P = 0.013). BNP-induced rises in burst incidence (bursts/100 beats), and burst area per 100 beats, however, were not significant. In conclusion, BNP infused at low doses that only had subtle effects on hemodynamics increased CSNA burst frequency and burst are per minute. This increase in CSNA may in large part be secondary to an increase in heart rate as CSNA burst incidence and burst area per 100 beats were not significantly increased. This study provides no evidence for inhibition of CSNA by natriuretic peptides.

Low-dose Atrial Natriuretic Peptide for Chronic Kidney Disease in Coronary Surgery

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease. We investigated the effectiveness of human atrial natriuretic peptide (hANP) infusion in CKD patients undergoing coronary artery bypass grafting (CABG). We analyzed 134 consecutive cases in which CABG had been performed in our hospital from 2002 to 2005. They were divided into four groups: Group A (n = 19) was CKD + placebo, Group B (n = 30) was non-CKD + placebo, Group C (n = 22) was CKD + hANP, and Group D (n = 63) was non-CKD + hANP). The serum creatinine (mg/dl) and estimated glomerular filtration rate (ml/min/1.73 m²) were measured as evaluation values. The value of sCr changed preoperatively and at 1 year postoperatively from 1.09 ± 0.09, 51.3 ± 4.4 to 1.26 ± 0.42, 49.4 ± 14.4 in Group A, from 0.77 ± 0.14, 75.5 ± 12.1 to 0.91 ± 0.40, 72.3 ± 19.5 in Group B, from 0.99 ± 0.12, 54.8 ± 3.0 to 0.93 ± 0.16, 64.2 ± 12.3 in Group C and from 0.77 ± 0.13, 77.7 ± 13.4 to 0.83 ± 0.17, 75.9 ± 16.2 in Group D, respectively. There was a significant difference between Group A and Group C regarding the change of creatinine (p =0.0022). Our study has confirmed that an infusion of hANP during CABG in patients with CKD not only improves perioperative renal function, but also prevents the progression of CKD.

Atrial natriuretic peptide for preventing and treating acute kidney injury

Acute kidney injury (AKI) is common in hospitalised patients and is associated with significant morbidity and mortality. Despite recent advances, outcomes have not substantially changed in the last four decades. Atrial natriuretic peptide (ANP) has shown promise in animal studies, however randomised controlled trials (RCTs) have shown inconsistent clinical benefits. To assess the benefits and harms of ANP for preventing and treating AKI. We searched CENTRAL, MEDLINE and EMBASE and reference lists of retrieved articles. RCTs that investigated all forms of ANP versus any other treatment in adult hospitalised patients with or "at risk" of AKI. Results were expressed as risk ratios (RR) with 95% confidence intervals (CI) or mean difference (MD). Outcomes were analysed separately for low and high dose ANP for preventing or treating AKI. Nineteen studies (11 prevention, 8 treatment; 1,861 participants) were included. There was no difference in mortality between ANP and control in either the low or high dose prevention studies. Low (but not high) dose ANP was associated with a reduced need for RRT in the prevention studies (RR 0.32, 95% CI 0.14 to 0.71). Length of hospital and ICU stay were significantly shorter in the low dose ANP group. For established AKI, there was no difference in mortality with either low or high dose ANP. Low (but not high) dose ANP was associated with a reduction in the need for RRT (RR 0.54, 95% CI 0.30 to 0.98). High dose ANP was associated with more adverse events (hypotension, arrhythmias). After major surgery there was a significant reduction in RRT requirement with ANP in the prevention studies (RR 0.56, 95% CI 0.32 to 0.99), but not in the treatment studies. There was no difference in mortality between ANP and control in either the prevention or treatment studies. There was a reduced need for RRT with low dose ANP in patients undergoing cardiovascular surgery (RR 0.35, 95% CI 0.18 to 0.70). ANP was not associated with outcome improvement in either radiocontrast nephropathy or oliguric AKI. ANP may be associated with improved outcomes when used in low doses for preventing AKI and in managing postsurgery AKI and should be further explored in these two settings. There were no significant adverse events in the prevention studies, however in the high dose ANP treatment studies there were significant increases hypotension and arrhythmias.

Differential Regulation of Endothelial Cell Permeability by cGMP via Phosphodiesterases 2 and 3

Endothelial barrier dysfunction leading to increased permeability and vascular leakage is an underlying cause of several pathological conditions, including edema and sepsis. Whereas cAMP has been shown to decrease endothelial permeability, the role of cGMP is controversial. Endothelial cells express cGMP-inhibited phosphodiesterase (PDE)3A and cGMP-stimulated PDE2A. Thus we hypothesized that the effect of cGMP on endothelial permeability is dependent on the concentration of cGMP present and on the relative expression levels of PDE2A and PDE3A. When cAMP synthesis was slightly elevated with a submaximal concentration of 7-deacetyl-7-(O-[N-methylpiperazino]-gamma-butyryl)-dihydrochloride-forskolin (MPB-forskolin), we found that low doses of either atrial natriuretic peptide (ANP) or NO donors potentiated the inhibitory effects of MPB-forskolin on thrombin-induced permeability. However, this inhibitory effect of forskolin was reversed at higher doses of ANP or NO. These data suggest that cGMP at lower concentrations inhibits PDE3A and thereby increases a local pool of cAMP, whereas higher concentrations cGMP activates PDE2A, reversing the effect. Inhibitors of PDE3A mimicked the effect of low-dose ANP on thrombin-induced permeability, and inhibition of PDE2A reversed the stimulation of permeability seen with higher doses of ANP. Finally, increasing PDE2A expression with tumor necrosis factor-alpha reversed the inhibition of permeability caused by low doses of ANP. As predicted, the effect of tumor necrosis factor-alpha on permeability was reversed by a PDE2A inhibitor. These findings suggest that the effect of increasing concentrations of cGMP on endothelial permeability is biphasic, which, in large part, is attributable to the relative amounts of PDE2A and PDE3A in endothelial cells.

Differential Regulation of Endothelial Cell Permeability by cGMP via Phosphodiesterases 2 and 3

Endothelial barrier dysfunction leading to increased permeability and vascular leakage is an underlying cause of several pathological conditions, including edema and sepsis. Whereas cAMP has been shown to decrease endothelial permeability, the role of cGMP is controversial. Endothelial cells express cGMP-inhibited phosphodiesterase (PDE)3A and cGMP-stimulated PDE2A. Thus we hypothesized that the effect of cGMP on endothelial permeability is dependent on the concentration of cGMP present and on the relative expression levels of PDE2A and PDE3A. When cAMP synthesis was slightly elevated with a submaximal concentration of 7-deacetyl-7-( O -[ N -methylpiperazino]-γ-butyryl)-dihydrochloride–forskolin (MPB–forskolin), we found that low doses of either atrial natriuretic peptide (ANP) or NO donors potentiated the inhibitory effects of MPB–forskolin on thrombin-induced permeability. However, this inhibitory effect of forskolin was reversed at higher doses of ANP or NO. These data suggest that cGMP at lower concentrations inhibits PDE3A and thereby increases a local pool of cAMP, whereas higher concentrations cGMP activates PDE2A, reversing the effect. Inhibitors of PDE3A mimicked the effect of low-dose ANP on thrombin-induced permeability, and inhibition of PDE2A reversed the stimulation of permeability seen with higher doses of ANP. Finally, increasing PDE2A expression with tumor necrosis factor-α reversed the inhibition of permeability caused by low doses of ANP. As predicted, the effect of tumor necrosis factor-α on permeability was reversed by a PDE2A inhibitor. These findings suggest that the effect of increasing concentrations of cGMP on endothelial permeability is biphasic, which, in large part, is attributable to the relative amounts of PDE2A and PDE3A in endothelial cells.

Continuous Low-Dose Human Atrial Natriuretic Peptide Promotes Diuresis in Oliguric Patients After Living Donor Liver Transplantation

Continuous Low-Dose Human Atrial Natriuretic Peptide Promotes Diuresis in Oliguric Patients After Living Donor Liver Transplantation

Atrial Natriuretic Peptide Has Dose‐Dependent, Autonomically Mediated Effects on Atrial Refractoriness and Repolarization in Anesthetized Dogs

Atrial natriuretic peptide (ANP) may alter electrophysiological properties of the heart and possibly have a role in arrhythmogenesis. However, previous studies have yielded conflicting results and have not fully considered whether ANP's cardiac electrophysiological effects are mediated via direct actions and/or indirectly via the autonomic nervous system. This study's aim was to establish whether ANP infused at pathophysiological and pharmacological doses has significant in vivo cardiac electrophysiological effects and to determine whether these effects are directly or autonomically mediated. Electrophysiologic and hemodynamic effects of ANP infusion (human ANP at 15-600 ng/kg per minute) were examined in chloralose-anesthetized dogs under conditions of varying autonomic blockade. In autonomically intact dogs (n = 12), low-dose ANP (15 ng/kg per minute) shortened atrial effective refractory period (ERP) (P < 0.001) and monophasic action potential duration (MAPD90) (P < 0.05) at 600, 500, and 400 msec atrial paced cycle lengths and reduced right atrial pressure (P < 0.05) but did not alter mean arterial pressure. After either combined vagal and beta-adrenergic blockade (vagotomy plus atropine plus propranolol, n = 7) or selective vagal blockade (n = 9), low-dose ANP no longer altered atrial ERP or MAPD90. Higher ANP doses (150 and 600 ng/kg per minute) decreased mean arterial and right atrial pressures (P < 0.001) but did not alter atrial ERP, MAPD90, or other electrophysiological parameters including atrial fibrillation threshold, ventricular ERP, and MAPD90. ANP has dose-dependent, autonomically mediated effects on atrial refractoriness and repolarization.

Vascular, renal, and endocrine responses to low-dose atrial natriuretic peptide in the fluid-balanced New Zealand genetically hypertensive rats with and without endogenous arginine vasopressin

In hypertension, the relationship between atrial natriuretic peptide (ANP) and vasopressin (AVP) is not yet clear, although their renal actions are effectively autoregulation. To examine the possible interaction further, the responses to ANP infusion (75 ng x min (-1), i.v.) have been investigated in both hypertensive and normotensive AVP-replete (HT and NT) and AVP-deficient (HTDI and NTDI) rats. This study aimed to assess the renal function and the plasma hormone concentrations of AVP, angiotensin II (AII), ANP, aldosterone, and corticosterone in the conscious, chronically catheterized, fluid-balanced rats, and to examine the cardiovascular, renal, and endocrine responses to a constant infusion of a low-dose ANP. Data gained from the present study showed, for the first time, the hormone profile, plasma electrolyte composition, and detailed renal function of the servo-controlled, fluid-balanced rats. The similarities of plasma electrolyte composition between servo-controlled and untreated rats indicated that the servo-controlled fluid replacement technique maintained the differences between the strains and maintained body fluid balance during the experimental periods. Following ANP administration, there were no changes in glomerular filtration rate (GFR) in all groups, but an enduring diuresis and natriuresis were observed in HT and NT, which were milder in HTDI rats. However, the hypotensive effect of ANP was of a similar magnitude in all rat strains. HTDI rats exhibited an inhibition of the renin-angiotensin system (RAS), which may have participated in the reduced mean arterial blood pressure (MAP) and natriuresis observed in these rats. The renal actions of ANP appear to rely upon renal tubular events, as indicated by increased fractional electrolyte excretions in the AVP-replete rats. This study highlights the importance of AVP to the profile of the renal actions of ANP in normal rats.

Vascular, renal, and endocrine responses to low-dose atrial natriuretic peptide in the fluid-balanced New Zealand genetically hypertensive rats with and without endogenous arginine vasopressin

In hypertension, the relationship between atrial natriuretic peptide (ANP) and vasopressin (AVP) is not yet clear, although their renal actions are effectively autoregulation. To examine the possible interaction further, the responses to ANP infusion (75 ng x min (-1), i.v.) have been investigated in both hypertensive and normotensive AVP-replete (HT and NT) and AVP-deficient (HTDI and NTDI) rats. This study aimed to assess the renal function and the plasma hormone concentrations of AVP, angiotensin II (AII), ANP, aldosterone, and corticosterone in the conscious, chronically catheterized, fluid-balanced rats, and to examine the cardiovascular, renal, and endocrine responses to a constant infusion of a low-dose ANP. Data gained from the present study showed, for the first time, the hormone profile, plasma electrolyte composition, and detailed renal function of the servo-controlled, fluid-balanced rats. The similarities of plasma electrolyte composition between servo-controlled and untreated rats indicated that the servo-controlled fluid replacement technique maintained the differences between the strains and maintained body fluid balance during the experimental periods. Following ANP administration, there were no changes in glomerular filtration rate (GFR) in all groups, but an enduring diuresis and natriuresis were observed in HT and NT, which were milder in HTDI rats. However, the hypotensive effect of ANP was of a similar magnitude in all rat strains. HTDI rats exhibited an inhibition of the renin-angiotensin system (RAS), which may have participated in the reduced mean arterial blood pressure (MAP) and natriuresis observed in these rats. The renal actions of ANP appear to rely upon renal tubular events, as indicated by increased fractional electrolyte excretions in the AVP-replete rats. This study highlights the importance of AVP to the profile of the renal actions of ANP in normal rats.

Atrial natriuretic peptide increases urinary albumin excretion in men with Type 1 diabetes mellitus and established microalbuminuria

Raised plasma concentrations of atrial natriuretic peptide (ANP) have been reported in patients with Type 1 (insulin dependent) diabetes mellitus (DM) who have poor glycaemic control and are associated with the presence of microalbuminuria. To test the hypothesis that elevations in plasma ANP concentration increase urinary albumin excretion in Type 1 DM, we have studied the effects of intravenous infusions of ANP in eight such subjects with established microalbuminuria. Blood glucose was maintained between 4 and 7 mmol l−1 in all subjects for the duration of studies; after euglycaemia had been established, a standard oral water load (20 ml kg−1 plus replacement of urinary losses) was given. Once steady state diuresis was attained, subjects received intravenous infusion of either placebo (0.9 % saline), low dose (2.5 pmol kg−1 min−1) or high dose (5.0 pmol kg−1 kg min−1) ANP solution in a randomized, double-blind protocol. Infusion of ANP caused a dose-dependent increase in urinary albumin excretion rate (placebo, 11.3 (SD 8.9) to 8.7 (SD 6.8) μg min−1; low dose ANP, 12.4 (SD 9.9) to 26.5 (SD 27.5) μg min−1, p < 0.01; high dose ANP 10.3 (SD 7.3) to 36.6 (SD 28.5) μg min−1, p < 0.001, ANOVA). Only high dose ANP caused an increase in urine flow. Blood glucose remained unchanged in all studies. We conclude that intravenous infusions of ANP cause a dose-dependent increase in urinary albumin excretion rate in Type 1 DM subjects with microalbuminuria. These data support the hypothesis that ANP has albuminuric actions which may contribute to microalbuminuria in Type 1 DM. © 1998 John Wiley & Sons, Ltd.

Atrial Natriuretic Peptide and Brain Natriuretic Peptide in Cor Pulmonale: Hemodynamic and Endocrine Effects

Atrial Natriuretic Peptide and Brain Natriuretic Peptide in Cor Pulmonale: Hemodynamic and Endocrine Effects

Atrial natriuretic peptide replacement therapy in rats subjected to biatrial appendectomy

Atrial natriuretic peptide replacement therapy in rats subjected to biatrial appendectomy

Pressure‐dependent, enhanced natriuretic response to low‐dose, atrial natriuretic peptide infusion in essential hypertension

To examine whether the effect of atrial natriuretic peptide (ANP) on renal glomerular and tubular segmental handling of sodium in patients with essential hypertension is pressure dependent. Part 1. The renal effects of a low-dose continuous infusion (10 ng kg-1 min-1) with ANP for 1 h were compared in 10 untreated essential hypertensives (EH) and 13 normotensive control subjects (CS). Part 2. The hypertensives were studied on another day with ANP infusion during preceding acute BP reduction with sodium nitroprusside infusion (NP). The results were compared with those obtained during infusion with ANP+placebo (Part 1). Lithium clearance was used to estimate the proximal tubular reabsorption of sodium. Part 1. Atrial natriuretic peptide caused an exaggerated increase in urinary sodium excretion (+102 vs. +38%: P < 0.05), fractional excretion of sodium (+80 vs. +37%: P < 0.05), and urinary output (+56 vs. +8.3%; P < 0.05) in EH compared with CS. Glomerular filtration rate and filtration fraction increased to the same degree in both groups. Absolute lithium clearance (CLi) increased and FELi tended to increase (P = 0.061) in EH, but these were unchanged in CS. The increase in plasma cyclic guanosine 5'-phosphate (cGMP) and urinary excretion of cGMP and the decrease in plasma aldosterone during ANP infusion were the same in the two groups. Part 2. During NP infusion the natriuresis caused by ANP in EH was reduced (+51 vs. +99%; P < 0.05). The relative changes in GFR, CLi, and FELi during ANP infusion were not affected by the preceding BP reduction with NP. Mean arterial pressure was reduced from 122 to 101 mmHg during NP infusion. The relative increase in sodium excretion in EH was significantly correlated to mean arterial pressure. Low-dose ANP infusion causes an exaggerated natriuresis in untreated essential hypertensives due to a more pronounced reduction in tubular reabsorption. After BP reduction, the natriuresis induced by ANP in essential hypertensives is decreased, probably due to a less pronounced reduction in tubular reabsorption beyond the proximal tubules. We suggest that the enhanced natriuretic response to ANP in EH in secondary in some degree to the elevated systemic pressure.