High-dose Atrial Natriuretic Peptide Research Articles

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.

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.

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

Effects of Nitrendipine on Sodium Balance During Changes in Sodium Intake and Low-Dosage ANP

We found previously that calcium entry blockade with nitrendipine enhanced the natriuretic effect of high-dose atrial natriuretic peptide (ANP). It is unknown whether nitrendipine also influences the effect of physiological changes in ANP. We therefore studied the effect of nitrendipine on cumulative sodium balance during changes in sodium intake as well as on natriuresis after low-dosage ANP infusion during low and high sodium (LS and HS, respectively) intake. In eight healthy volunteers, sodium balance was recorded after the switch from LS (20 mmol/day) to HS (300 mmol/day) diet. Cumulative sodium balance was equal with (441 +/- 45 mmol) or without (458 +/- 45 mmol) nitrendipine treatment. The body weight curves were also fully congruent. ANP (0.005 micrograms/kg/min for 3 h) was administered during maximal water diuresis on both sodium intake levels with and without nitrendipine. Infusion of ANP increased sodium excretion (mumol/min) from 30 +/- 7 to 81 +/- 12 (LS) and from 316 +/- 27 to 469 +/- 46 (HS). During nitrendipine, similar increments (from 36 +/- 7 to 98 +/- 24 mumol/min, HS) were found. ANP had no effect on inulin clearance and fractional excretion of lithium, but consistently depressed diluting segment reabsorption. This pattern was also similar during nitrendipine. Apparently, under the conditions of this study in normal subjects, nitrendipine has no effect on sodium balance. ANP, in physiological concentrations, increases natriuresis mainly by depressing sodium reabsorption in the distal nephron, an effect not enhanced by nitrendipine.

Atrial natriuretic peptide attenuates the development of pulmonary hypertension in rats adapted to chronic hypoxia.

To test the hypothesis that chronic infusion of atrial natriuretic peptide (ANP) instituted before hypoxic exposure attenuates the development of pulmonary hypertension in hypoxia adapted rats, ANP (0.2 and 1.0 microgram/h) or vehicle was administered intravenously via osmotic minipump for 4 wk beginning before exposure to 10% O2 or to room air. Low dose ANP increased plasma ANP levels by only 60% of vehicle controls after 4 wk and significantly decreased mean pulmonary arterial pressure (MPAP) (P less than 0.01), the ratio of right ventricular weight to body weight (RV/BW) (P less than 0.01), and the wall thickness of small (50-100 microns) pulmonary arteries (P = 0.01) in hypoxia-adapted rats. ANP did not alter any of these parameters in air-control rats. High dose ANP increased plasma ANP levels by 230% of control and produced greater reductions in MPAP (P less than 0.001) and RV/BW) (P less than 0.05), but not in pulmonary arterial wall thickness, than the low dose. Neither dose of ANP altered mean systemic arterial pressure in either hypoxic or normoxic rats. The data demonstrate that chronic infusion of exogenous ANP at a dose that does not affect MPAP or RV weight in air-control rats attenuates the development of pulmonary hypertension and RV enlargement in rats adapted to chronic hypoxia.

Intracerebroventricular Atrial Natriuretic Peptide Infusion Augments the Adrenocorticotropin and Angiotensin II Responses to Hemorrhage in Sheep

The central actions of atrial natriuretic peptide (ANP) in rats include inhibition of arginine vasopressin (AVP) release, and less consistently, ACTH suppression and hypotension. To explore any such inhibitory actions on basal and stimulated levels of AVP and ACTH, we have studied the effect of intracerebroventricular (ICV) infusion of ANP on the hemodynamic and hormonal response to acute hemorrhage in conscious sheep. Two groups of 5 sheep received rat ANP(101-126) by ICV infusion (0.5 microgram bolus followed by 0.5 microgram/h for 3 h, or 5 micrograms bolus followed by 5 micrograms/h for 3 h) as well as artificial cerebrospinal fluid control infusions in random order. One hour after the start of the ICV infusion, acute hemorrhage (15 ml/kg BW within 10 min) was performed. Basal levels before hemorrhage of mean arterial pressure (MAP), heart rate and plasma hormones were unaltered by either dose of ICV ANP. After hemorrhage, the fall in MAP and rise in heart rate were similar in each group. However, compared to control infusions the response to hemorrhage of ACTH (433 +/- 147 to 2,175 +/- 588 vs. control 541 +/- 103 to 893 +/- 244 ng/l; p less than 0.016) and angiotensin II (AII) (18 +/- 3 to 94 +/- 23 vs. control 18 +/- 4 to 58 +/- 8 pmol/l; p less than 0.001) were significantly greater during high-dose ANP infusion. Although peak AVP levels more than doubled those observed on the control day, the increase did not reach statistical significance (p less than 0.1053). Plasma concentration of cortisol, aldosterone, epinephrine and norepinephrine were not significantly different in control and ANP-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)