Interactions of atrial and brain natriuretic peptides at pathophysiological levels in normal men

1995 ◽  
Vol 269 (6) ◽  
pp. R1397-R1403 ◽  
Author(s):  
P. J. Hunt ◽  
E. A. Espiner ◽  
A. M. Richards ◽  
T. G. Yandle ◽  
C. Frampton ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Sodium Excretion ◽  
Urine Volume ◽  
Random Order ◽  
Normal Male ◽  
Metabolic Clearance ◽  
Physiological Effects ◽  
Brain Natriuretic Peptides ◽  
Normal Humans ◽  
Normal Men

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are both circulating plasma hormones that are secreted by the heart and have similar physiological effects. We have shown previously that abrupt increases in plasma BNP in normal humans impair the clearance of ANP from plasma and result in additive physiological effects. Because large increases in plasma ANP are reported to have no effect on plasma BNP levels in patients with heart failure, we have studied ANP-BNP interactions in eight normal male subjects receiving background infusions of BNP (2 pmol.kg-1.min-1 for 5 h). Each subject also received a coinfusion of ANP ("active" day, 2 pmol.kg-1.min-1 for 2 h) or vehicle ("placebo" day) using a balanced random order, single-blind design. Metabolic clearance rate of ANP (mean 4.1 +/- 0.6 l/min) and disappearance rate from the plasma (t1/2 3.4 +/- 0.3 min) were similar to values measured previously in the absence of exogenous BNP. In contrast, steady-state plasma BNP levels were reversibly increased (mean BNP increment 10 pmol/l) during the administration of ANP (P = 0.038). Associated with these changes were significant (additive) physiological effects. Thus the addition of ANP increased plasma and urine guanosine 3',5'-cyclic monophosphate (P < 0.001 for both) and lowered systolic blood pressure (P = 0.049). When ANP was coinfused, significant differences were also observed in urine volume (P = 0.001) and sodium excretion (P = 0.043) between the infusion period (when urine volume and sodium excretion were enhanced) and postinfusion period (when values decreased). Taken together, our findings of similar interactions between ANP-BNP and BNP-ANP infusions occurring at pathophysiological concentrations of these two peptides, suggest that the interactions result from dissociation of prebound hormone, presumably from biological or clearance receptors.

Comparative Bioactivity of Atrial and Brain Natriuretic Peptides in An Ovine Model of Heart Failure

1997 ◽  
Vol 92 (2) ◽  
pp. 159-165 ◽  
Author(s):  
Miriam Tessa Rademaker ◽  
Christopher John Charles ◽  
Eric Arnold Espiner ◽  
Christopher Miles Frampton ◽  
Michael Gary Nicholls ◽  
...  
Keyword(s):  
Heart Failure ◽  
Natriuretic Peptide ◽  
Urine Volume ◽  
Peripheral Resistance ◽  
Pressure Control ◽  
Guanosine Monophosphate ◽  
Metabolic Clearance ◽  
Ovine Model ◽  
Metabolic Clearance Rate ◽  
Brain Natriuretic Peptides

1. Whereas many studies have detailed the effects of exogenous atrial natriuretic peptide (ANP) infusions in heart failure, and a limited number have examined the effects of brain natriuretic peptide (BNP), none have directly compared the bioactivity of similar doses of ANP and BNP under standard conditions of impaired cardiac function. We compared the hormonal, haemodynamic and renal effects of 3 h infusions of ANP, BNP and a vehicle control in eight sheep with pacing-induced heart failure (225 beats/min for 8–12 days). 2. Infusion of ANP and BNP increased plasma ANP (P < 0.001) (276 ± 27 versus control 142 ± 26 pmol/l) and BNP (P < 0.001) (257 ± 34 versus control 45 ± 5 pmol/l) respectively, in association with increased cyclic 3′,5′-guanosine monophosphate [control, 40 ± 6; ANP, 53 ± 6 (P < 0.05); BNP, 57 ± 7 nmol/l (P < 0.001)]. Metabolic clearance rate and half-life were similar for both peptides. Infusion of ANP and BNP similarly reduced mean arterial pressure [control, 73.0 ± 1.6; ANP, 67.6 ± 1.2 (P < 0.01); BNP, 65.7 ± 1.7 mmHg (P < 0.001)], left atrial pressure (both P < 0.05) (control, 22.0 ± 0.7; ANP, 19.9 ± 1.0; BNP, 19.8 ± 0.9 mmHg) and peripheral resistance [control, 50.3 ± 4.1 mmHg l−1 min−1; ANP, 46.0 ± 2.8 (P < 0.05); BNP, 43.8 ± 4.5 (P < 0.01)], and increased urine volume (2-3-fold, both P < 0.05), sodium excretion (> 10-fold, both P < 0.01) and haematocrit levels relative to control (both P < 0.05). Infused BNP tended to raise plasma ANP levels (by 28 pmol/l), while ANP increased plasma BNP (by 18 pmol/l). Plasma aldosterone was reduced by approximately 40% by both peptides (both P < 0.05). 3. In conclusion, ANP and BNP are both powerfully natriuretic, similarly suppress aldosterone and appear equipotent in reducing preload and after-load in this model of pacing-induced heart failure.

Renal, endocrine, and hemodynamic interactions of atrial and brain natriuretic peptides in normal men

1994 ◽  
Vol 266 (4) ◽  
pp. R1244-R1250 ◽  
Author(s):  
C. M. Florkowski ◽  
A. M. Richards ◽  
E. A. Espiner ◽  
T. G. Yandle ◽  
C. Frampton
Keyword(s):  
Heart Failure ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Plasma Levels ◽  
Plasma Catecholamines ◽  
Random Order ◽  
Metabolic Clearance ◽  
Sympathetic Nervous Systems ◽  
Mild Heart Failure ◽  
Normal Men

Brain natriuretic peptide (BNP) is a recently identified hormone that is secreted by the human heart and circulates in plasma with natriuretic, endocrine, and hemodynamic effects similar to those of atrial natriuretic peptide (ANP). To examine the interaction of human BNP with ANP, we studied eight normal men receiving constant infusions of ANP (2.0 pmol.kg-1.min-1 for 5 h), with and without superimposed infusions of BNP (2.0 pmol.kg-1.min-1 for 2 h), using a balanced random-order design. BNP infusions achieved plasma levels of 30-35 pmol/l at 90-120 min and were similar to levels observed in mild heart failure. Metabolic clearance rate of BNP (mean 4.6 +/- 0.4 l/min) and disappearance rate from plasma (t1/2 18.9 min) were similar to values determined previously in the absence of exogenous ANP. In contrast, the addition of BNP induced a progressive and reversible increase (50%) in steady-state plasma ANP. Compared with ANP alone, BNP induced an additional (50%) increase in sodium excretion (P < 0.05) and significant increases in both plasma (P < 0.001) and urine guanosine 3',5'-cyclic monophosphate (P < 0.01). Systolic blood pressure was lowered by the addition of BNP (P < 0.01) and continued to fall after cessation of BNP infusions. Despite this, the response of the renin-aldosterone and sympathetic nervous systems (heart rate and plasma catecholamines) was not significantly different on the two study days. As well as showing additive effects of the two natriuretic peptides, these studies point to important interactions of BNP on ANP metabolism at plasma levels observed in mild heart failure.

Atrial Natriuretic Peptide, Altitude and Acute Mountain Sickness

1989 ◽  
Vol 77 (5) ◽  
pp. 509-514 ◽  
Author(s):  
J. S. Milledge ◽  
J. M. Beeley ◽  
S. McArthur ◽  
A. H. Morice
Keyword(s):  
Body Weight ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Packed Cell Volume ◽  
Sodium Excretion ◽  
Acute Mountain Sickness ◽  
Urine Volume ◽  
Symptom Scores ◽  
Mountain Sickness ◽  
Atrial Natriuretic

1. To investigate the mechanisms of acute mountain sickness, 22 subjects travelled to 3100 m by road and the following day walked to 4300 m on Mount Kenya. Control measurements were made over 2 days at 1300 m before ascent and for 2 days after arrival at 4300 m. These included body weight, 24 h urine volume, 24 h sodium and potassium excretion, blood haemoglobin, packed cell volume, and symptom score for acute mountain sickness. In 15 subjects blood samples were taken for assay of plasma aldosterone and atrial natriuretic peptide. 2. Altitude and the exercise in ascent resulted in a marked decrease in 24 h urine volume and sodium excretion. Aldosterone levels were elevated on the first day and atrial natriuretic peptide levels were higher on both altitude days compared with control. 3. Acute mountain sickness symptom scores showed a significant negative correlation with 24 h urinary sodium excretion on the first altitude day. Aldosterone levels tended to be lowest in subjects with low symptom scores and higher sodium excretion. No correlation was found between changes in haemoglobin concentration, packed cell volume, 24 h urine volume or body weight and acute mountain sickness symptom score. 4. Atrial natriuretic peptide levels at low altitude showed a significant inverse correlation with acute mountain sickness symptom scores on ascent.

Atrial natriuretic peptide in preeclampsia: metabolic clearance, sodium excretion and renal hemodynamics

1997 ◽  
Vol 273 (3) ◽  
pp. F483-F487 ◽  
Author(s):  
D. W. Irons ◽  
P. H. Baylis ◽  
T. J. Butler ◽  
J. M. Davison
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Sodium Excretion ◽  
Renal Plasma Flow ◽  
Metabolic Clearance ◽  
Significant Difference ◽  
Basal Plasma ◽  
Natriuretic Effect ◽  
Atrial Natriuretic

To further elucidate the role of atrial natriuretic peptide (ANP) in preeclampsia, its metabolic clearance (MCRANP) was determined concomitantly with its effects on sodium excretion (UNa), glomerular filtration rate (GFR), and effective renal plasma flow (ERPF). Ten untreated preeclamptic primigravidae (PET) were studied at 29-37 wk gestation and again 4 mo postpartum (PP). Basal plasma concentration of ANP was significantly increased in PET compared with PP (14.8 +/- 1.9 vs. 4.1 +/- 0.5 pmol/l, respectively; P < 0.0001). MCRANP in PET and PP was 5.0 +/- 0.8 and 4.9 +/- 0.5 l/min [not significant (NS)], respectively. In PET, infusion of ANP produced (basal vs. ANP) a natriuresis (UNa 0.14 +/- 0.02 vs. 0.28 +/- 0.04 mmol/min, P < 0.001) and an increase in GFR (97 +/- 7 vs. 106 +/- 8 ml/min, P < 0.05), with ERPF unchanged (609 +/- 24 vs. 634 +/- 29 ml/min, NS). In PP, ANP infusion also produced a natriuresis (UNa 0.20 +/- 0.02 vs. 0.25 +/- 0.02 mmol/min, P = 0.01), no significant change in GFR (109 +/- 7 vs. 102 +/- 4 ml/min), and a significant reduction in ERPF (514 +/- 22 vs. 409 +/- 18 ml/min, P < 0.0001). Analysis of variance demonstrated a greater natriuretic effect of ANP in PET compared with PP (P < 0.05), similarly a significant difference in the effect of ANP on ERPF (P < 0.01) and GFR (P < 0.05) was seen but not on filtration fraction (P = 0.35).

scholarly journals Brain Natriuretic Peptide and Neutral Endopeptidase Inhibition in Left Ventricular Impairment1

1999 ◽  
Vol 84 (2) ◽  
pp. 723-729 ◽  
Author(s):  
John G. Lainchbury ◽  
A. Mark Richards ◽  
M. Gary Nicholls ◽  
Eric A. Espiner ◽  
Timothy G. Yandle
Keyword(s):  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Combined Treatment ◽  
Plasma Renin ◽  
Random Order ◽  
Hypotensive Effect ◽  
Neutral Endopeptidase ◽  
Left Ventricular ◽  
Metabolic Clearance ◽  
Nep Inhibition

Brain natriuretic peptide (BNP) is increased in left ventricular impairment and neutral endopeptidase (NEP) is involved in its metabolism. In random order, eight patients with left ventricular impairment received placebo, a 4-h infusion of human BNP (3.0 pmol/kg min), a single oral dose of NEP inhibitor (SCH 42495, 300 mg), and combined BNP and SCH 42495. Plasma BNP, cGMP, and cortisol were significantly increased by all three treatments (P &lt; 0.05–P &lt; 0.001). Combined treatment had a synergistic effect on plasma cGMP. The metabolic clearance rate of exogenous BNP was reduced (25%) by NEP inhibition. Endogenous plasma ANP was augmented more than BNP by NEP inhibition. Plasma aldosterone, unchanged during infusions, rose markedly after BNP and after the combined treatment (P &lt; 0.05 for both). Urine sodium excretion, increased by NEP inhibition (P &lt; 0.05) and by BNP (P = 0.05), was unchanged during combined treatment. Urine cGMP excretion was increased, whereas blood pressure was reduced by all active treatments (P &lt; 0.05–0.01 for all). Heart rate increased only with combined treatment (P = 0.007). Plasma renin activity, norepinephrine, and cardiac output were unaffected. BNP infusion and NEP inhibition both induced significant hemodynamic and renal responses. The augmented hypotensive effect of combined treatments, and consequent fall in renal perfusion pressure, may underly the observed blunting of the natriuretic response that occurred despite greater than additive increments in plasma BNP, ANP, and cGMP.

Dissociation between plasma atrial natriuretic peptide levels and urinary sodium excretion after intravenous saline infusion in normal man

1987 ◽  
Vol 73 (3) ◽  
pp. 285-289 ◽  
Author(s):  
Donald R. J. Singer ◽  
Angela C. Shore ◽  
Nirmala D. Markandu ◽  
Martin G. Buckley ◽  
Giuseppe A. Sagnella ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Sodium Excretion ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Saline Infusion ◽  
Sodium Balance ◽  
Normal Male ◽  
Maximal Rise ◽  
Atrial Natriuretic

1. Plasma immunoreactive atrial natriuretic peptide (ANP) and urinary sodium excretion were measured in six normal male subjects before, during and for 195 min after a 60 min infusion of 2 litres of saline (0.9% NaCl, 308 mmol of Na+). 2. During the saline infusion, there was a significant increase in plasma ANP and urinary sodium excretion and a significant decrease in plasma renin activity, aldosterone, albumin, creatinine and packed cell volume. 3. The maximal rise in mean plasma ANP occurred 15 min after stopping the infusion and the maximal rise in mean urinary sodium excretion in the collection period 30 min later. 4. Plasma ANP then decreased so that by the end of the study the level was the same as before the saline infusion. However, at this time, 195 min after the saline infusion was stopped, there was still a net positive sodium balance of 220 mmol and urinary sodium excretion remained significantly elevated. 5. Our results are compatible with the concept that increased ANP secretion may play a role in the immediate increase in sodium excretion after a saline load. However, they also suggest that other mechanisms may be more important for the longer term increase in sodium excretion.

Evidence for tissue diffusion limitation of VO2max in normal humans

1989 ◽  
Vol 67 (1) ◽  
pp. 291-299 ◽  
Author(s):  
J. Roca ◽  
M. C. Hogan ◽  
D. Story ◽  
D. E. Bebout ◽  
P. Haab ◽  
...  
Keyword(s):  
Venous Blood ◽  
Random Order ◽  
Work Load ◽  
Gas Analysis ◽  
Co2 Production ◽  
Diffusion Limitation ◽  
Normal Humans ◽  
Normal Men ◽  
Tissue Diffusion ◽  
Mixed Venous

We recently found [at approximately 90% maximal O2 consumption (VO2max)] that as inspiratory PO2 (PIO2) was reduced, VO2 and mixed venous PO2 (PVO2) fell together along a straight line through the origin, suggesting tissue diffusion limitation of VO2max. To extend these observations to VO2max and directly examine effluent venous blood from muscle, six normal men cycled at VO2max while breathing air, 15% O2 and 12% O2 in random order on a single day. From femoral venous, mixed venous, and radial arterial samples, we measured PO2, PCO2, pH, and lactate and computed mean muscle capillary PO2 by Bohr integration between arterial (PaO2) and femoral venous PO2 (PfvO2). VO2 and CO2 production (VCO2) were measured by expired gas analysis, VO2max averaged 61.5 +/- 6.2 (air), 48.6 +/- 4.8 (15% O2), and 38.1 +/- 4.1 (12% O2) ml.kg-1.min-1. Corresponding values were 16.8 +/- 5.6, 14.4 +/- 5.0, and 12.0 +/- 5.0 Torr for PfVO2; 23.6 +/- 3.2, 19.1 +/- 4.2, and 16.2 +/- 3.5 Torr for PVO2; and 38.5 +/- 5.4, 30.3 +/- 4.1, and 24.5 +/- 3.6 Torr for muscle capillary PO2 (PmCO2). Each of the PO2 variables was linearly related to VO2max (r = 0.99 each), with an intercept not different from the origin. Similar results were obtained when the subjects were pushed to a work load 30 W higher to ensure that VO2max had been achieved. By extending our prior observations 1) to maximum VO2 and 2) by direct sampling of femoral venous blood, we conclude that tissue diffusion limitation of VO2max may be present in normal humans. In addition, since PVO2, PfVO2, and PmCO2 all linearly relate to VO2max, we suggest that whichever of these is most readily obtained is acceptable for further evaluation of the hypothesis.

Abstract P476: 8-Aminoguanosine Exerts Diuretic and Natriuretic Activity via Conversion to 8-Aminoguanine

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Edwin K Jackson ◽  
Zaichuan Mi
Keyword(s):  
Intravenous Administration ◽  
Sodium Excretion ◽  
Antihypertensive Drugs ◽  
Urine Volume ◽  
Systemic Circulation ◽  
Tandem Mass ◽  
Contralateral Kidney ◽  
New Class ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

We previously reported that 8-aminoguanosine and 8-aminoguanine are potent and efficacious K + -sparing diuretics/natriuretics that may represent a new class of antihypertensive drugs. Moreover, because these compounds are endogenous, they may have physiological roles. It is possible that the diuretic/natriuretic activity of 8-aminoguanosine is mediated mostly via conversion to 8-aminoguanine. To test this concept, we conducted 3 protocols in anesthetized rats. The 1 st protocol demonstrated that at 85 to 115 min post intravenous administration, both 8-aminoguanosine and 8-aminoguanine (33.5 μmol/kg) significantly increased urine volume [ml/min: 8-aminoguanosine from 0.3 ± 0.1 to 0.9 ± 0.1 (mean ± SEM; n=7); 8-aminoguanine from 0.3 ± 0.1 to 1.5 ± 0.2 (n=8)] and sodium excretion (μmol/min: 8-aminoguanosine from 12 ± 6 to 109 ± 21; 8-aminoguanine from 18 ± 8 to 216 ± 31). The 2 nd protocol showed that intrarenal artery infusions of 8-aminoguanosine (from 0.1 to 1 μmol/kg/min) did not affect urine volume or sodium excretion in either the ipsilateral or contralateral kidney. In contrast, intrarenal artery infusions of 8-aminoguanine significantly increased ipsilateral (but not contralateral) urine volume [at 1 μmol/kg/min from 0.2 ± 0.02 to 0.7 ± 0.1 (n=17)] and sodium excretion (from 24 ± 4 to 216 ± 31). In a 3 rd protocol we administered 8-aminoguanosine and 8-aminoguanine intravenously (33.5 μmol/kg) and measured renal interstitial (medulla) levels of 8-aminoguanosine and 8-aminoguanine using microdialysis combined with ultraperformance liquid chromatography-tandem mass spectrometry. Intravenous administration of 8-aminoguanosine and 8-aminoguanine similarly increased renal interstitial levels of 8-aminoguanine [ng/ml; 8-aminoguanosine from 4 ± 1 to 1025 ± 393 (n=6), and 8-aminoguanine from 2 ± 1 to 1069 ± 407 (n=6)]. Neither 8-aminoguanosine nor 8-aminoguanine affected renal interstitial levels of 8-aminoguanosine. Together these data clearly show that the renal effects of 8-aminoguanosine are not direct, but require conversion in the systemic circulation to 8-aminoguanine. If 8-aminoguanosine is physiologically important it should be viewed as a “pro-hormone.” As a pharmacological agent, it is best described as a “pro-drug.”

Association of B-Type Natriuretic Peptide Level with Residual Kidney Function in Incident Peritoneal Dialysis Patients

2019 ◽  
Vol 39 (2) ◽  
pp. 147-154 ◽  
Author(s):  
Yasuhiro Kawai ◽  
Shigeru Tanaka ◽  
Hisako Yoshida ◽  
Masatoshi Hara ◽  
Hiroaki Tsujikawa ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Kidney Function ◽  
Natriuretic Peptide ◽  
Subgroup Analysis ◽  
Proportional Hazards Model ◽  
Urine Volume ◽  
Cox Proportional Hazards Model ◽  
University Hospital ◽  
Residual Kidney Function ◽  
Increased Risk

Background Residual kidney function (RKF) is an important factor influencing both technique and patient survival in peritoneal dialysis (PD) patients. B-type natriuretic peptide (BNP) is considered a marker of cardio-renal syndrome. The relationship between BNP and RKF in PD patients remains unclear. Methods We conducted a prospective study of 89 patients who had started and continued PD for 6 months or more in Kyushu University Hospital between June 2006 and September 2015. Participants were divided into low BNP (≤ 102.1 ng/L) and high BNP (> 102.1 ng/L) groups according to median plasma BNP level at PD initiation. The primary outcome was RKF loss, defined as 24-hour urine volume less than 100 mL. We estimated the association between BNP and RKF loss using a Kaplan-Meier method and Cox proportional hazards model and compared the rate of RKF decline between the 2 groups. To evaluate the consistency of the association, we performed subgroup analysis stratified by baseline characteristics. Results During the median follow-up of 30 months, 30 patients lost RKF. Participants in the high BNP group had a 5.87-fold increased risk for RKF loss compared with the low BNP group after adjustment for clinical and cardiac parameters. A high plasma BNP level was more clearly associated with RKF loss in younger participants compared with older participants in subgroup analysis. Conclusions B-type natriuretic peptide may be a useful risk marker for RKF loss in PD patients. The clinical importance of plasma BNP level as a marker of RKF loss might be affected by age.

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