scholarly journals B-type natriuretic peptide 8-32, which is produced from mature BNP 1-32 by the metalloprotease meprin A, has reduced bioactivity

2009 ◽  
Vol 296 (6) ◽  
pp. R1744-R1750 ◽  
Author(s):  
Guido Boerrigter ◽  
Lisa C. Costello-Boerrigter ◽  
Gail J. Harty ◽  
Brenda K. Huntley ◽  
Alessandro Cataliotti ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Urinary Sodium Excretion ◽  
Urine Flow ◽  
Peptide Sequence ◽  
Right Atrial ◽  
Pulmonary Capillary ◽  
Urinary Potassium ◽  
Potential Strategy ◽  
Wedge Pressure

32-amino acid B-type natriuretic peptide (BNP 1-32) plays an important role in cardiovascular homeostasis. Recently, it was reported that BNP 1-32 is cleaved by the metalloprotease meprin A to BNP 8-32, the bioactivity of which is undefined. We hypothesized that BNP 8-32 has reduced vasodilating and natriuretic bioactivity compared with BNP 1-32 in vivo. Human BNP 8-32 and BNP 1-32 were compared in a crossover study in eight anesthetized normal canines. After a preinfusion clearance, BNP 1-32 was infused at 30 ng·kg−1·min−1 for 45 min followed by a 60-min washout and a second preinfusion clearance. Then, equimolar BNP 8-32 was infused. In half of the studies, the peptide sequence was reversed. Changes with peptides from the respective preinfusion clearance to infusion clearance were compared with paired tests. Mean arterial pressure was reduced by both BNP 8-32 and BNP 1-32 (−8 ± 3 vs. −6 ± 2 mmHg, P = 0.48). Changes in right atrial pressure, pulmonary capillary wedge pressure, heart rate, cardiac output, and glomerular filtration rate were similar. However, urinary sodium excretion increased less with BNP 8-32 than with BNP 1-32 (+171 ± 24 vs. +433 ± 43 μEq/min; P = 0.008), as did urinary potassium excretion, urine flow, and renal blood flow. While BNP 8-32 has similar vasodilating actions as BNP 1-32, its diuretic and natriuretic actions are reduced, suggesting a role for meprin A in the regulation of BNP 1-32 bioactivity in the kidney. Meprin A inhibition may be a potential strategy to increase the bioactivity of endogenous and exogenous BNP 1-32 in cardiovascular diseases.

Des-serine-proline brain natriuretic peptide 3–32 in cardiorenal regulation

2007 ◽  
Vol 292 (2) ◽  
pp. R897-R901 ◽  
Author(s):  
Guido Boerrigter ◽  
Lisa C. Costello-Boerrigter ◽  
Gail J. Harty ◽  
Harald Lapp ◽  
John C. Burnett
Keyword(s):  
Amino Acids ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Urinary Sodium Excretion ◽  
Urine Flow ◽  
Accelerated Degradation ◽  
Equimolar Dose ◽  
Terminal Amino ◽  
Physiologic Role

Brain natriuretic peptide (BNP 1–32) plays an important physiologic role in cardiorenal homeostasis. Recently, it has been reported that BNP 1–32 is rapidly cleaved by the ubiquitous enzyme dipeptidyl peptidase IV to BNP 3–32, which lacks the two NH2-terminal amino acids of BNP 1–32. The bioactivity of BNP 3–32 in cardiorenal regulation is unknown. We hypothesized that BNP 3–32 has reduced vasodilating and natriuretic bioactivity compared with BNP 1–32 in vivo. Synthetic human BNP 3–32 and BNP 1–32 were administered to eight anesthetized normal canines. After baseline measurements, BNP 1–32 at 30 ng·kg−1·min−1 was administered, followed by a washout, a postinfusion clearance, and a clearance with an equimolar dose of BNP 3–32. In four studies, the sequence of BNP 1–32 and BNP 3–32 infusion was reversed. Peptides were compared by analyzing the changes from the respective preinfusion clearance to the respective infusion clearance. * P < 0.05 between peptides. BNP 3–32, unlike BNP 1–32, did not decrease mean arterial pressure (0 ± 1 vs. −7 ± 2* mmHg, respectively) and did not increase renal blood flow (+12 ± 10 vs. +52 ± 10* ml/min). Effects on heart rate and cardiac output were similar. Urinary sodium excretion increased 128 ± 18 μeq/min with BNP 3–32 and 338 ± 40* μeq/min with BNP 1–32. Urine flow increased 1.1 ± 0.2 ml/min with BNP 3–32 and 2.8 ± 0.4* ml/min with BNP 1–32. Plasma BNP immunoreactivity was lower with BNP 3–32, suggesting accelerated degradation. In this study, BNP 3–32 showed reduced natriuresis and diuresis and a lack of vasodilating actions compared with BNP 1–32.

Activation of myocardial and renal natriuretic peptides during acute intravascular volume overload in dogs: functional cardiorenal responses to receptor antagonism

1998 ◽  
Vol 95 (2) ◽  
pp. 195-202 ◽  
Author(s):  
Daniel D. BORGESON ◽  
Tracy L. STEVENS ◽  
Denise M. HEUBLEIN ◽  
Yuzuru MATSUDA ◽  
John C. BURNETT
Keyword(s):  
Pulmonary Capillary Wedge Pressure ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Volume Overload ◽  
Treated Group ◽  
Atrial Pressure ◽  
Right Atrial ◽  
Intravascular Volume ◽  
Pulmonary Capillary ◽  
Wedge Pressure

1.A family of structurally related but genetically distinct natriuretic peptides exist which include atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) of myocardial cell origin and C-type natriuretic peptide (CNP) of endothelial and renal epithelial cell origin. All three exert actions via cGMP, with ANP and BNP functioning via the natriuretic peptide A receptor and CNP via the natriuretic peptide B receptor. 2.Circulating and urinary natriuretic peptides were determined in response to acute intravascular volume overload (AVO). Additionally, their functional role in cardiorenal regulation during AVO was investigated by utilizing the natriuretic peptide receptor antagonist HS-142-1. Control (n = 5) and study dogs (HS-142-1, n = 9) underwent AVO with normal saline equal to 10% of body weight over 1 ;h. Both groups demonstrated similar significant increases in right atrial pressure, pulmonary capillary wedge pressure, pulmonary artery pressure and cardiac output. Circulating ANP paralleled increases in right atrial pressure and pulmonary capillary wedge pressure, with no changes in plasma BNP or CNP. At peak AVO, urinary CNP excretion was increased compared with baseline (7.0±4.2 versus 62±8.0 ;pg/min, P< 0.05). 3.In the HS-142-1-treated group, plasma cGMP was decreased compared with the control group (9.6±1.1 to 5.0±1.2 ;pmol/ml, P< 0.05). A significant attenuation of natriuresis (566±91 versus 1241±198 ;μEq/min, P< 0.05) and diuresis (4.8±0.7 versus 10.1±2.0 ;ml/min, P< 0.05) was also observed at peak AVO in the HS-142-1 treated group. 4.These findings support differential and selective responses of the three natriuretic peptides to AVO, in which plasma ANP and urinary CNP are markers for AVO. Secondly, these studies confirm the role of ANP and CNP but not BNP in the natriuretic and diuretic response to acute volume overload.

scholarly journals P1429 B-Type natriuretic peptide prediction of right catheterization parameters in the first year after heart transplant

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
A A Valentim Goncalves ◽  
T Pereira-Da-Silva ◽  
R Soares ◽  
L De Sousa ◽  
R Ilhao Moreira ◽  
...  
Keyword(s):  
Cardiac Index ◽  
Pulmonary Artery ◽  
Pulmonary Capillary Wedge Pressure ◽  
Pulmonary Vascular Resistance ◽  
Natriuretic Peptide ◽  
Pulmonary Artery Pressure ◽  
Right Atrial ◽  
First Year ◽  
Pulmonary Capillary ◽  
Wedge Pressure

Abstract Introduction Despite being the gold-standard for hemodynamic assessment, right heart catheterization (RHC) was overcome by plasma B-Type Natriuretic Peptide (BNP) levels in daily clinical routine. However, in the first year after heart transplantation (HT), the relationship between BNP and adverse hemodynamics have yielded conflicting results. Purpose The aim of this study was to evaluate whether BNP values can be used to estimate adverse hemodynamics in the first year after HT. Methods Prospective study of consecutive RHC performed in the first year after HT (according to the endomyocardial biopsies program). Plasma BNP levels were measured at the same day. The area under the curve (AUC) was analysed to find the BNP values with higher sensitivity and specificity to detect adverse hemodynamics. Results From 2017 to 2018, 50 RHC were performed. Mean age was 48.7 ± 8.3 years, with mean BNP value of 964.4 ± 1114.7pg/ml. Prediction of adverse hemodynamics by AUC results are represented in the table. BNP values were significantly increased in patients with pulmonary capillary wedge pressure (PCWP) &gt;12mmHg (p &lt; 0.001), cardiac index &lt;2.5L/min/m2 (p = 0.001), mean pulmonary artery pressure (mPAP) ≥25mmHg (p &lt; 0.001), pulmonary vascular resistance &gt; 1,5WU (p = 0.044) and right atrial pressure &gt;5mmHg (p = 0.003). BNP &gt;500pg/ml had a sensitivity of 78.3% and 87.5% and a specificity of 76.0% and 67.7% to detect PCWP &gt;12mmHg and mPAP ≥25mmHg, respectively. Conclusion Significant associations were found between BNP values and adverse hemodynamics in RHC, supporting the clinical utility of BNP in the first year after HT. BNP prediction AUC values SR HEMODYNAMIC PARAMETERS AUC p 95% CI Best BNP value Sensitivity Specificity Pulmonary capillary wedge pressure (PCWP) &gt; 12mmHg 0.798 &lt;0.001 0.671-0.925 &gt; 500pg/ml 78.3% 76.0% Mean pulmonary artery pressure (mPAP) ≥ 25mmHg 0.830 &lt;0.001 0.714-0.946 &gt; 500pg/ml 87.5% 67.7% Cardiac output &lt; 4L/min 0.833 0.002 0.667-1.000 &gt; 1500pg/ml 77.8% 87.5% Cardiac index (CI) &lt; 2.5L/min/m2 0.810 0.001 0.663-0.957 &gt; 1150pg/ml 76.9% 86.1% Pulmonary vascular resistance (PVR) &gt; 1,5WU 0.678 0.044 0.509-0.848 &gt; 200pg/ml 83.3% 47.1% Right atrial pressure (RAP) &gt; 5mmHg 0.744 0.003 0.607-0.880 &gt; 500pg/ml 70.8% 65.4% BNP prediction

Haemodynamic and Hormonal Responses to Cardiac Pacing in Humans: Influence of Different Stimulation Sequences and Rates

1995 ◽  
Vol 88 (2) ◽  
pp. 165-172 ◽  
Author(s):  
Hans Berglund ◽  
Anders Edlund ◽  
Elvar Theodorsson ◽  
Hans Vallin
Keyword(s):  
Plasma Concentration ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Atrial Pressure ◽  
Right Atrial ◽  
Pulmonary Capillary ◽  
Peptide Release ◽  
Arterial Plasma ◽  
Wedge Pressure ◽  
Atrial Natriuretic

1. To examine the effects of rate and pressure on release of vasoactive hormones, 10 healthy subjects were examined. 2. A standardized pacing protocol was used to achieve different haemodynamic responses at two predetermined heart rates. Haemodynamic variables, and plasma concentrations of atrial natriuretic peptide, arginine vasopressin, adrenaline and noradrenaline were measured. 3. Right atrioventricular pacing at a rate of 150 impulses/min resulted in disparate responses in right atrial pressure (slight decrease) and pulmonary capillary wedge pressure (increase). Change in arterial plasma concentration of atrial natriuretic peptide correlated to change in pulmonary capillary wedge pressure, and change in arterial plasma concentration of noradrenaline correlated to change in total systemic vascular resistance, whereas concentrations of adrenaline and arginine vasopressin did not alter significantly during the stimulation periods. A significant influence of rate in addition to the pressure related influence on plasma concentration of atrial natriuretic peptide was found. In contrast, an increase in rate in the absence of an increase in atrial pressures did not raise the plasma concentration of atrial natriuretic peptide. There was no significant relationship between change in atrial natriuretic peptide and noradrenaline. 4. These data support the concept of a rate dependence of atrial natriuretic peptide release in man. Increased atrial pressure and thus presumed atrial stretch seems to be a prerequisite for increased plasma concentration of atrial natriuretic peptide. In addition, these results highlight the importance of monitoring both left and right atrial pressure in clinical investigations assessing modulation of atrial natriuretic peptide release.

Role of atrial natriuretic peptide in volume-expansion natriuresis

1986 ◽  
Vol 251 (2) ◽  
pp. R310-R313 ◽  
Author(s):  
T. R. Schwab ◽  
B. S. Edwards ◽  
D. M. Heublein ◽  
J. C. Burnett
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Sodium Excretion ◽  
Volume Expansion ◽  
Fractional Excretion ◽  
Urinary Sodium Excretion ◽  
Urine Flow ◽  
Urinary Sodium ◽  
Right Atrial ◽  
Fractional Excretion Of Sodium

Studies were performed to investigate the role of circulating atrial natriuretic peptide (ANP) in acute volume-expansion natriuresis. Sham-operated (SHAM, n = 6) and right atrial appendectomized (ATRX, n = 12) anesthetized rats underwent acute volume expansion with isoncotic albumin. After equilibration and control periods, volume expansion increased urine flow rate, urinary sodium excretion, fractional excretion of sodium, and circulating ANP. Absolute increases in urine flow rate (delta 46 +/- 4 SHAM; delta 25 +/- 5 microliter/min ATRX), urinary sodium excretion (delta 9.48 +/- 1.01 SHAM; delta 4.77 +/- 1.03 mueq/min ATRX), fractional excretion of sodium (delta 3.16 +/- 0.53 SHAM; delta 1.65 +/- 0.32% ATRX), and ANP (delta 303.3 +/- 35.9 SHAM; delta 156.6 +/- 26.0 pg/ml ATRX) were significantly reduced by right atrial appendectomy. No significant differences in mean arterial pressure, central venous pressure, or glomerular filtration rate during volume expansion were observed between groups. These studies support the hypothesis that right atrial appendectomy in the rat attenuates acute volume expansion-induced increases in circulating ANP and urinary sodium excretion and that the natriuresis of acute volume expansion is mediated in part by an increase in circulating ANP.

Hemodynamic and renal effects of low-dose infusions of atrial peptide in awake dogs

1988 ◽  
Vol 254 (2) ◽  
pp. R161-R169 ◽  
Author(s):  
P. Bie ◽  
B. C. Wang ◽  
R. J. Leadley ◽  
K. L. Goetz
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Sodium Excretion ◽  
Plasma Renin ◽  
Urine Flow ◽  
Right Atrial ◽  
Experimental Protocols ◽  
Cardiac Filling ◽  
Left And Right ◽  
Atrial Natriuretic

The effects of alpha-human atrial natriuretic peptide (alpha-hANP) on cardiovascular and renal function in conscious dogs were evaluated in two experimental protocols. In one protocol, alpha-hANP was infused intravenously at increasing rates of 50, 100, and 200 ng.min-1.kg-1 (stepup infusion) during successive 20-min periods. The greatest responses occurred during the final 20-min period of the stepup infusion when the plasma concentration of immunoreactive atrial natriuretic peptide (irANP) was increased by 44-fold over preinfusion values; pressures in the aorta and both atria were decreased at this time, whereas glomerular filtration rate, urine flow, and sodium excretion were increased. In a second protocol, alpha-hANP was infused for 1 h at constant rates of either 12.5, 25, or 50 ng.min-1.kg-1; these constant infusions increased plasma irANP by 3-, 7-, and 12-fold, respectively. Each infusion rate decreased left and right atrial pressures and increased urine flow and sodium excretion. The two lowest infusion rates elevated plasma irANP to levels that would be expected to occur only during unusual physiological, or perhaps pathophysiological, conditions. The two highest infusion rates decreased plasma renin activity. Nevertheless, the accompanying maximal increases in sodium excretion were modest (41-72%). These data imply that small changes in circulating atrial peptides that presumably occur under normal physiological conditions would not have a dominant effect on the regulation of sodium excretion; the peptides may, however, play a modulatory role on sodium excretion under these conditions. It remains to be determined whether the ability of atrial peptides to lower cardiac filling pressures is of physiological significance.

scholarly journals ANP-mediated inhibition of distal nephron fractional sodium reabsorption in wild-type and mice overexpressing natriuretic peptide receptor

2010 ◽  
Vol 298 (1) ◽  
pp. F103-F108 ◽  
Author(s):  
Di Zhao ◽  
Kailash N. Pandey ◽  
L. Gabriel Navar
Keyword(s):  
Natriuretic Peptide ◽  
Sodium Excretion ◽  
Urinary Sodium Excretion ◽  
Sodium Reabsorption ◽  
Natriuretic Peptide Receptor ◽  
Distal Nephron ◽  
Peptide Receptor ◽  
Natriuretic Peptide Receptor A ◽  
Npr1 Gene

Atrial natriuretic peptide (ANP) elicits natriuresis; however, the relative contributions of proximal and distal nephron segments to the overall ANP-induced natriuresis have remained uncertain. This study was performed to characterize the effects of ANP on distal nephron sodium reabsorption determined after blockade of the two major distal nephron sodium transporters with amiloride (5 μg/g body wt) plus bendroflumethiazide (12 μg/g body wt) in male anesthetized C57/BL6 and natriuretic peptide receptor-A gene (Npr1) targeted four-copy mice. The lower dose of ANP (0.1 ng·g body wt−1·min−1, n = 6) increased distal sodium delivery (DSD, 2.4 ± 0.4 vs. 1.6 ± 0.2 μeq/min, P < 0.05) but did not change fractional reabsorption of DSD compared with control (86.3 ± 2.0 vs. 83.9 ± 3.6%, P > 0.05), thus limiting the magnitude of the natriuresis. In contrast, the higher dose (0.2 ng·g body wt−1·min−1, n = 6) increased DSD (2.8 ± 0.3 μeq/min, P < 0.01) and also decreased fractional reabsorption of DSD (67.4 ± 4.5%, P < 0.01), which markedly augmented the natriuresis. In Npr1 gene-duplicated four-copy mice ( n = 6), the lower dose of ANP increased urinary sodium excretion (0.6 ± 0.1 vs. 0.3 ± 0.1 μeq/min, P < 0.05) and decreased fractional reabsorption of DSD compared with control (72.2 ± 3.4%, P < 0.05) at similar mean arterial pressures (91 ± 6 vs. 92 ± 3 mmHg, P > 0.05). These results provide in vivo evidence that ANP-mediated increases in DSD alone exert modest effects on sodium excretion and that inhibition of fractional reabsorption of distal sodium delivery is requisite for the augmented natriuresis in response to the higher dose of ANP or in Npr1 gene-duplicated mice.

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