Plasma Atrial Natriuretic Peptide Concentrations Research Articles

Increased Plasma Atrial Natriuretic Peptide after Ingestion of Low Doses of Ethanol in Humans

Previous studies have demonstrated that, in human, acute consumption of high doses of ethanol, administered in a large quantity of fluid, with or without volume-loading, induced either a decrease or an increase in the plasma content of atrial natriuretic peptide (ANP)--a substance that has a hypotensive effect. The objective of the present study was to examine the effect of low doses of ethanol (0, 0.25, and 0.50 g of ethanol/kg of body weight) administered to six normotensive individuals, in a small volume of fluid without prior volume-loading. Before and at various intervals after administration of the placebo or ethanol drinks, heart rate and blood pressure were measured and blood samples were taken for estimation of the plasma ANP, arginine vasopressin, and cortisol contents. Results indicated small changes in blood pressure and heart rate after ingestion of either the placebo or ethanol drinks. On the other hand, a significant increase in the plasma ANP content was observed at 15 min after ingestion of both the 0.25 and 0.50 g of ethanol/kg of body weight doses, but not after the placebo drink. Plasma ANP levels were still elevated at 45 min postethanol intake, but had returned to basal levels at 120 min after the ethanol drink. Interestingly, it was noticed that the higher dose of ethanol (0.50 g) did not induce a higher plasma ANP concentration than the lower dose (0.25 g) of ethanol; however, the plasma ANP content remained elevated for a longer period. Furthermore, the increase in plasma ANP content was not due to ethanol or stress-induced increases in the plasma arginine vasopressin and cortisol contents, because the plasma concentration of these hormones remained either at basal or below basal levels for the duration of the experiment. In conclusion, ingestion of low amounts of ethanol equivalent to 1 or 2 standard drinks induced an increase in plasma ANP content.

Increased Plasma Atrial Natriuretic Peptide after Ingestion of Low Doses of Ethanol in Humans

Previous studies have demonstrated that, in human, acute consumption of high doses of ethanol, administered in a large quantity of fluid, with or without volume-loading, induced either a decrease or an increase in the plasma content of atrial natriuretic peptide (ANP)—a substance that has a hypotensive effect. The objective of the present study was to examine the effect of low doses of ethanol (0,0.25, and 0.50 g of ethanoVkg of body weight) administered to six normoten-sive individuals, in a small volume of fluid without prior volume-loading. Before and at various intervals after administration of the placebo or ethanol drinks, heart rate and blood pressure were measured and blood samples were taken for estimation of the plasma ANP, arginine vasopressin, and cortisol contents. Results indicated small changes in blood pressure and heart rate after ingestion of either the placebo or ethanol drinks. On the other hand, a significant increase in the plasma ANP content was observed at 15 min after ingestion of both the 0.25 and 0.50 g of ethanol/kg of body weight doses, but not after the placebo drink. Plasma ANP levels were still elevated at 45 min postethanol intake, but had returned to basal levels at 120 min after the ethanol drink. Interestingly, it was noticed that the higher dose of ethanol (0.50 g) did not induce a higher plasma ANP concentration than the lower dose (0.25 g) of ethanol; however, the plasma ANP content remained elevated for a longer period. Furthermore, the increase in plasma ANP content was not due to ethanol or stress-induced increases in the plasma arginine vasopressin and cortisol contents, because the plasma concentration of these hormones remained either at basal or below basal levels for the duration of the experiment. In conclusion, ingestion of low amounts of ethanol equivalent to 1 or 2 standard drinks induced an increase in plasma ANP content.

Plasma levels of atrial natriuretic peptide and endothelin-1 in experimental fat embolism.

In order to understand the role of vasoactive peptides in fat embolism, arterial plasma atrial natriuretic peptide (ANP) and endothelin-1 concentrations were investigated in an experimental study. Nine anesthetized and mechanically ventilated pigs received an intracaval infusion of allogeneic bone marrow suspension at a dose of 100 mg/kg (fat embolism group); 9 control pigs received saline. The observation period was 5 h. In the fat embolism group, cardiac index and heart rate decreased within 30 min, whereas mean arterial pressure remained stationary. Pulmonary capillary wedge pressure rose transiently and central venous pressure rose slightly in time, while mean pulmonary arterial pressure, pulmonary vascular resistance and pulmonary shunt increased immediately and persistently after the bone marrow suspension infusion. Simultaneously, arterial oxygen tension and arterial hemoglobin oxygen saturation decreased markedly. Arterial plasma ANP and endothelin-1 concentrations remained stable in the fat embolism animals, whereas in the controls ANP and endothelin-1 levels decreased at 3 and 5 h. Arterial epinephrine concentrations were stable in animals receiving bone marrow suspension, while in the controls arterial epinephrine concentrations decreased towards the end of the experiment. Arterial norepinephrine concentrations remained unchanged in both groups. To conclude, impaired pulmonary function and consequent systemic hypoxemia distinguish the present fat embolism model. Unchanged arterial ANP and endothelin-1 concentrations in the fat embolism group suggest that these circulating vasoactive hormones have a minor impact on the pathogenesis of the current experimental fat embolism.

Mechanism of attenuated thirst in aging: role of central volume receptors.

To test the hypothesis that the inhibitory action of central blood volume expansion on thirst and renal fluid regulation is attenuated with aging, we monitored the drinking and renal responses of dehydrated older (70 +/- 2 yr, n = 6) and younger (24 +/- 1 yr, n = 6) subjects during 195 min of head-out water immersion (HOI), which shifts blood centrally and increases plasma volume (PV). Subjects dehydrated by exercising for 2 h at 36 degrees C in the evening and refraining from fluids overnight before HOI in 34 degrees C water or a seated control in water perfusion suit [time control (TC)] the next morning. Ad libitum water intake was allowed after 15 min of HOI. Dehydration decreased PV by 10.6 +/- 1 and 7.3 +/- 1.8% (P < 0.05) and increased plasma osmolality by 6 +/- 2 and 7 +/- 1 mosmol/kg H2O (P < 0.05) in older and younger subjects, respectively. Thirst ratings increased in both groups, but pre-HOI thirst perception on a line rating scale was lower in older (69 +/- 8 mm) than younger (94 +/- 6 mm, P < 0.05) subjects. Fifteen minutes of HOI restored PV by 7.8 +/- 1.0 and 5.7 +/- 1.0% in older and younger subjects, respectively, but suppressed thirst rating in younger subjects only (P < 0.05). Fluid intake was reduced in HOI compared with TC in younger (6.3 +/- 0.5 vs. 14.3 +/- 2.2 ml/kg, P < 0.05) but not in older (6.7 +/- 2.1 vs. 8.4 +/- 3.3 ml/kg) subjects. During HOI, older subjects had smaller suppression of plasma renin activity and aldosterone concentration but a greater increase in the plasma atrial natriuretic peptide concentration (P[ANP], P < 0.05). HOI increased fractional sodium excretion in both groups, but mean arterial pressure increased only in the older subjects (P < 0.05). We conclude that the inhibitory influence of central volume expansion on thirst and drinking behavior is diminished with aging. Furthermore, in contrast to younger people, HOI natriuresis is associated with exaggerated increases in P[ANP] and arterial blood pressure in older people, suggesting arterial baroreceptors may be involved in the fluid regulatory response to central blood volume expansion in older people.

Correlations between ANP concentrations in atria, plasma and cerebral structures and sodium chloride preference in Wistar rats.

We determined whether ANP (atrial natriuretic peptide) concentrations, measured by radioimmunoassay, in the ANPergic cerebral regions involved in regulation of sodium intake and excretion and pituitary glad correlated with differences in sodium preference among 40 Wistar male rats (180-220 g). Sodium preference was measured as mean spontaneous ingestion of 1.5% NaCl solution during a test period of 12 days. The relevant tissues included the olfactory bulb (OB), the posterior and anterior lobes of the pituitary gland (PP and AP, respectively), the median eminence (ME), the medial basal hypothalamus (MBH), and the region anteroventral to the third ventricle (AV3V). We also measured ANP content in the right (RA) and left atrium (LA) and plasma. The concentrations of ANP in the OB and the AP were correlated with sodium ingestion during the preceding 24 h, since an increase of ANP in these structures was associated with a reduced ingestion and vice-versa (OB: r = -0.3649, P < 0.05; AP: r = -0.3291, P < 0.05). Moreover, the AP exhibited a correlation between ANP concentration and mean NaCl intake (r = -0.4165, P < 0.05), but this was not the case for the OB (r = 0.2422). This suggests that differences in sodium preference among individual male rats can be related to variations of AP ANP level. Earlier studies indicated that the OB is involved in the control of NaCl ingestion. Our data suggests that the OB ANP level may play a role mainly in day-to-day variations of sodium ingestion in the individual rat.

Pressure-heart rate responses to alpha-adrenergic stimulation and hormonal regulation in normotensive patients with obstructive sleep apnea.

Seven normotensive untreated patients with obstructive sleep apnea (OSA) and five control subjects without OSA were compared. Patients with cardiac dilation, chronic airflow limitation, liver and kidney disease, or diabetes mellitus were excluded. Change in pressure-heart rate relation to alpha-adrenergic stimulation (P-HRR), extracellular volume (ECV), and plasma volume (Vp) were measured during daytime. Plasma atrial natriuretic peptide (ANP), plasma renin and aldosterone concentrations were obtained at 1 hour intervals during the night. A mean apnea/hypopnea index (AHI) of 52.2 +/- 23.9/h and a mean lowest arterial oxygen saturation (SaO2) of 61.2 +/- 19.3% (mean +/- SD) were determined from polysomnographic monitoring in the patient group. Release of ANP was significantly higher during sleep in OSA patients than in control subjects (P < .01), with a maximum concentration between 4 and 6 AM in the former. Daytime ECV was significantly higher (P < .05) and Vp significantly lower (P < .05) in OSA patients. Night maximum concentration of ANP (max ANP) was negatively related to AHI (P < .05). P-HRR was negatively related to AHI (P < .05) and positively related to max ANP (P < .05). In conclusion, OSA syndrome alters hormonal system control of body fluid compartment regulation. The decreased response in night max ANP secretion in the most severe OSA patients could be explained by the smaller Vp observed in these patients, decreasing atrial and ventricular pressure loading. Furthermore, alteration of P-HRR, correlated to AHI and max ANP, strengthens the hypothesis that patients who develop hypertension are those in whom the protective mechanism of ANP release failed.

Different Secretion Patterns of Adrenomedullin, Brain Natriuretic Peptide, and Atrial Natriuretic Peptide During Exercise in Hypertensive and Normotensive Subjects

The purpose of this study was to investigate the effect of exercise on plasma concentrations of adrenomedullin, brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) in patients with essential hypertension (n=15) and in normotensive controls (n=10). Exercise consisted of two fixed workloads, 40 and 80 watts of work load using a supine bicycle ergometer. Plasma levels of all three peptides at rest were significantly higher in hypertensives than in controls. Plasma concentrations of ANP increased with exercise in both groups and had greater

Changes in Plasma Atrial and Ventricular Natriuretic Peptide Concentrations after Transfer of Eels from Freshwater to Seawater or Vice Versa

Changes in plasma atrial and ventricular natriuretic peptide (ANP and VNP) concentrations were examined in conscious eels,Anguilla japonica,after transfer from freshwater (FW) to seawater (SW) or vice versa. These changes were compared in ventral and dorsal aortic blood since clearance receptors are present in the gills. Plasma Na concentration and osmolality in the ventral aortic blood rose linearly after transfer of FW eels to SW. Six hours after transfer, plasma ANP levels increased from 28.1 ± 2.9 to 44.8 ± 5.4 fmol/ml (n=6) (P<0.05) and plasma VNP levels also increased from 63.6 ± 3.8 to 91.2 ± 6.2 fmol/ml (n=6) (P<0.05). However, the levels gradually returned to the FW levels despite plasma Na concentration and osmolality remaining elevated. Dorsal aotic plasma ANP and VNP levels were unchanged after transfer of FW eels to SW, possibly due to extraction of secreted peptides by the branchial clearance receptors. After transfer of SW-adapted eels to FW, plasma ANP and VNP levels were unchanged, while both plasma Na concentration and osmolality decreased. These results indicate that plasma ANP and VNP levels are increased by an increase in plasma Na concentration or osmolality after transfer of FW eels to SW. However, the sustained increase in plasma Na concentration or osmolality no longer stimulated ANP and VNP secretion, and plasma ANP and VNP levels gradually returned to the FW levels gradually on adaptation to SW.

Natriuretic Peptides in Water-Deprived and in Salt-Loaded Rats

To elucidate the differences of physiological function of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), we measured tissue concentration and mRNA level in cardiac atrium, ventricle, and brain as well as plasma concentration of these three peptides in water-deprived (WD) and in salt-loaded (SL) rats. WD rats were given no water for 5 days, whereas SL rats had free access to 2% saline for 14 days. Plasma ANP and BNP concentration of the WD group decreased to 21% and < 10%, and the concentration of the SL group to 36% and 47% of the control (CON) group. Atrial and ventricular BNP concentration of the WD group decreased to 36% and 23% of the CON group, and atrial BNP concentration of the SL group decreased to a lesser extent. BNP mRNA level in atrium and ventricle decreased in both the WD and SL groups, with the WD group showing larger decreases to 11% and 20% of the CON group ANP mRNA level in atrium and ventricle of the WD group decreased to 40% and 61% of the CON group, but increased to 147% in ventricle of the SL group. In the brain, no significant change was observed in ANP and CNP concentration in both the WD and SL group. Under these conditions, BNP generally showed larger changes than ANP in both peptide concentration and mRNA level. Gene transcription and peptide production of ANP and BNP in atrium and in ventricle were not always found to be in concert, especially in the case of salt loading. Taken as a whole, our results demonstrate differences among the systems regulating biosynthesis and secretion of ANP and BNP in atrium and ventricle.

Mechanisms contributing to renal resistance to atrial natriuretic peptide in rats with common bile-duct ligation.

Blunted volume expansion (VE) natriuresis and renal resistance to atrial natriuretic peptide (ANP) characterize states of pathological sodium retention. This study examined rats 1 to 3 wk after common bile-duct ligation (CBDL), at which time they had hyperbilirubinemia and hypoalbuminemia. Sham-operated normal rats (Sham) showed an increased sodium excretion rate (UNaV) from 1.0 +/- 0.1 to 16.3 +/- 3.9 muEq/min in response to acute VE (iv saline, 2 mL/100 g body wt over 5 min), whereas CBDL rats had a blunted response that was apparent after 1 wk and became maximal at 2 and 3 wk (0.3 +/- 0.1 to 3.2 +/- 0.4 muEq/min at 3 wk, P < 0.01 versus Sham response). The peak urinary cGMP excretion rate (UcGMPV) was also blunted (37.9 +/- 3.6 versus 87.5 +/- 8.3 pmol/min, P < 0.01) despite an even greater increase in plasma ANP concentration (Sham, 9.6 +/- 0.4 pg/mL in hydropenia to 22.8 +/- 2.6 pg/mL after VE; CBDL, 15.3 +/- 2.3 to 41.8 +/- 6.8 pg/mL). ANP-dependent cGMP accumulation by isolated inner medullary collecting duct (IMCD) cells from both Sham and CBDL rat kidneys was dose-dependent; however, at higher concentrations of ANP (> 10(-8) M), accumulation by cells from CBDL rats was significantly blunted, indicating resistance to ANP. Binding of 125I-ANP to IMCD cells was not different in CBDL rats compared with Sham control rats. Renal denervation improved but did not completely reverse the blunted natriuresis, and ANP resistance persisted in IMCD cells from denervated kidneys of CBDL rats. Incubation of IMCD cells with the phosphodiesterase inhibitors isomethylbutylxanthine or Zaprinast (each at 10(-3) M) restored ANP responsiveness in both innervated and denervated kidneys from CBDL rats, and intrarenal infusion of Zaprinast (10 micrograms/min) corrected the blunted increase in UNaV and UcGMPV after VE in rats with CBDL. These results suggest that ANP resistance in a model of abnormal sodium metabolism devoid of intrinsic renal disease may be related to increased activity of phosphodiesterase in renal target cells for ANP as well as to heightened renal nerve activity.

Increased renal atrial natriuretic peptide synthesis in rats with deoxycorticosterone acetate-salt treatment.

To investigate the role of renal synthesis of atrial natriuretic peptide (ANP) as a contributor to the water-sodium homeostasis, we studied the effects of electrolyte-water imbalance on renal ANP mRNA levels, plasma ANP concentrations, and urinary ANP excretion rates by using reverse transcription-polymerase chain reaction (PCR) and radioimmunoassay. Male Wistar rates divided into the following three groups: 1) the control group, 2) deoxycorticosterone acetate (DOCA)-salt-treated group, and 3) low-salt-treated group. The urinary sodium excretion rate and urine volume in the DOCA-salt rats were significantly elevated at 2 days and for the 10-day study. The urinary ANP excretion rate in DOCA-salt rats was significantly increased at 2 days after treatment and was well correlated to the urinary sodium excretion rate (r = 0.76, P < 0.01). Plasma ANP levels in the DOCA-salt rats were elevated on the day of death. In contrast, plasma renin activities were markedly suppressed in DOCA-salt rats and increased in low-salt rats. By immunohistochemical study, immunoreactive ANP materials were mainly localized in the proximal and distal cortical tubules of the kidney. With the PCR cloning and sequencing technique, ANP cDNA was cloned from the rat kidney, and the sequences were identical to that of ANP identified in the atria. By semiquantitative PCR technique, the expression of ANP mRNA in the ventricle and renal cortex tissues was significantly enhanced in the DOCA-salt rats. Our results confirm that the rat kidney is a site of ANP synthesis and indicate that renal ANP synthesis is enhanced in a volume-expansion state. We propose that renal synthesized natriuretic peptide participates in the intrarenal regulation of water-electrolyte homeostasis and may contribute to renal adaptation during the mineralocorticoid escape phenomenon.

Haemodynamic and hormonal responses to long-term inhibition of nitric oxide synthesis in rats with portal hypertension

In portal hypertension, the role of the vasorelaxant nitric oxide (NO) in long-term splanchnic and systemic vascular tone regulation is unclear. This study examined the effects of long-term administration of a NO synthesis inhibitor on haemodynamics in portal hypertensive rats. Rats were randomly assigned to receive either water (placebo) or 100 mg/kg · day of oral N-nitro- l-arginine methylester ( l-NAME) for 28 days. At 14 days, the portal vein was ligated in 10 rats from each group. At 28 days, splanchnic and systemic blood flows were measured in 20 normal and 20 portal vein stenosed rats. Plasma atrial natriuretic peptide (ANP) concentrations as well as plasma and urinary cyclic guanosine monophosphate (cGMP) levels were also measured. Porto-systemic shunts were measured in other portal vein stenosed animals that had or had not received l-NAME. Portal vein stenosed rats that received l-NAME had significantly lower portal tributary blood flow and percentages of portal-systemic shunting (7.3 ± 0.5 versus 3.7 ± 0.2 ml/min · 100 g and 96 ± 1 versus 68 ± 5%, respectively) and higher hepatocollateral vascular resistance (147 ± 10 versus 295 ± 30 dyn · s · cm −5 · 100 g · 10 3, respectively) than placebo portal vein stenosed rats. Portal pressure, ANP and cGMP levels did not differ between the groups. Arterial pressure was significantly higher and cardiac index lower after l-NAME than after placebo. Normal rats had similar but less marked l-NAME-induced responses than portal hypertensive rats. The presence of a long-term l-NAME-induced vasoconstriction in collateral vessels and splanchnic and systemic arterioles in portal vein stenosed rats indicates that a NO-mediated vasodilator tone may contribute to the development and the maintenance of collateral circulation as well as splanchnic and systemic vasodilation in portal hypertension. Moreover, the NO-mediated vasodilator tone in portal hypertensive animals seems to be increased.

The adjustment of post-dialysis dry weight based on non-invasive measurements in children

The clinical criteria to assess hydration status are not always reliable. Hence, the development of techniques to estimate more accurately post-dialysis dry weight (DW) remains a major challenge. The present study evaluates the value of the inferior vena cava (IVC) diameter, plasma concentration of atrial natriuretic peptide (ANP), and plasma renin activity (PRA) in determining the DW in chronic haemodialysis children. Twelve overhydrated haemodialysis patients (4 girls, 8 boys) with a mean age of 12.8 were admitted to the study. Clinical, electrocardiographic, telecardiographic and echocardiographic findings, IVC and collapsibility indices and plasma concentrations of ANP and PRA were investigated before and after ultrafiltration (UF) therapy. Twelve age-matched normal children were studied as controls. Analysis of variance and Dunnett's test were applied for comparisons between patients and controls. Following UF therapy the patients' mean IVC collapsibility index was increased from 42.3 to 53.6% and IVC index was decreased from 1.08 to 0.81 cm/m2, both statistically significant. The pre-UF therapy collapsibility and IVC indices of the patient group were significantly different from those of the control group (56.9% and 0.70 cm/m2 respectively). The patients' mean plasma concentrations of ANP were 171 +/- 47.4 pg/ml before UF, 129 +/- 51.3 pg/ml after UF and 102 +/- 38.7 pg/ml in the control group. The ANP levels of the patients showed a significant decrease following the UF therapy. PRA was measured as 0.82 ng/ml/h before UF and 1.08 ng/ml/h after UF, but the increase was not statistically significant. Our findings revealed increased diameter of the IVC and plasma ANP concentrations and decreased collapsibility due to overhydration. Echography of IVC may be a promising non-invasive tool to estimate the DW in haemodialysis children. Further studies providing normative values for the IVC indices in both haemodialysis and normal children are required.

Regulation of the renal response to atrial natriuretic peptide by sodium intake in preweaned rats.

The neonate conserves sodium avidly, and sodium intake is normally limited to that present in maternal milk. To evaluate the role of atrial natriuretic peptide (ANP) in this adaptation, preweaned rat pups were artificially reared and fed a formula with either normal sodium (25 mEq/L) or high sodium (145 mEq/L) for 7-8 d. To determine whether increased dietary sodium decreases ANP clearance receptor activity, animals were anesthetized, and the plasma ANP concentration (ANPp), urine flow (V), urinary sodium (UNa V), and cGMP excretion (UcGMP V) were measured before and after infusion of ANF(4-23), an ANP clearance receptor inhibitor (C-ANF), at 50 micrograms/kg/ min. Infusion of C-ANF increased ANPp 10-fold in both normal and high sodium groups, but V, UNa V, and UcGMP V increased only in animals receiving the high sodium diet (p < 0.05). Incubation of isolated glomeruli with 0.1 microM ANP increased extracellular cGMP more in high sodium than normal sodium groups (p < 0.05). We conclude that ANP clearance receptors in the neonate are highly activated regardless of sodium intake. Increased dietary sodium increases the renal diuretic and natriuretic response to circulating ANP through enhanced generation of cGMP.

Dietary sodium intake modulates pituitary proopiomelanocortin mRNA abundance.

The pituitary prohormone proopiomelanocortin gives rise to melanocortins of alpha, beta, and gamma primary structure in addition to corticotropin. Melanocortins have a variety of actions in mammals, and each is natriuretic. In particular, gamma-melanocyte-stimulating hormone has been shown to mediate reflex natriuresis after acute unilateral nephrectomy. We examined whether this peptide could play a role in longer term adjustments in sodium balance by measuring plasma gamma-melanocyte-stimulating hormone and corticotropin concentrations, as well as pituitary proopiomelanocortin mRNA abundance, in Sprague-Dawley rats ingesting either a low (0.07% NaCl) or high (7.5% NaCl) sodium diet. One week after the high sodium diet, plasma gamma-melanocyte-stimulating hormone concentration was double the value seen in rats on the low sodium diet (158 +/- 5 [SE] versus 76 +/- 9 fmol/mL, P < .001), a change that was accompanied by a fivefold increase in plasma atrial natriuretic peptide concentration but no change in plasma corticotropin. Whole pituitary proopiomelanocortin mRNA abundance, measured with a probe to exon 3 of the rat proopiomelanocortin gene, was significantly increased after 1 week of the high sodium diet compared with the low sodium diet and increased further at 2 and 3 weeks. This increase occurred primarily in the neurointermediate lobe as demonstrated by in situ hybridization; the content of gamma-melanocyte-stimulating hormone immunoreactivity was also increased in this lobe, but not the anterior lobe, after 1 week of the high sodium diet. These results demonstrate that high dietary sodium intake increases neurointermediate lobe proopiomelanocortin mRNA abundance compared with a very low sodium diet and also suggest that proopiomelanocortin is preferentially processed into gamma-melanocyte-stimulating hormone rather than corticotropin. These observations consequently raise the possibility of a role for this peptide hormone system in the adjustments to a high salt diet.

Diagnostic Value of B-Type Natriuretic Peptide Concentrations in Patients With Acute Myocardial Infarction

Although elevations of plasma atrial natriuretic peptide (ANP) concentrations have been shown to have prognostic significance in patients after acute myocardial infarction (AMI), the relation between plasma levels of B-type natriuretic peptide (BNP) and cardiovascular mortality remains unknown. To test the prognostic value of plasma ANP and BNP after AMI, plasma concentrations were measured a mean of 3 days after infarction in 75 patients. During a median follow-up of 19.7 months, 14 patients (18.4%) died of cardiovascular causes. On univariate analysis, plasma ANP and BNP, Killip class, modified Peel index, left ventricular ejection fraction, and presence of left ventricular failure were all associated with cardiovascular mortality. In contrast, plasma ANP was the only variable that correlated with the development of symptomatic heart failure and hospitalization. For the combined end point of cardiovascular mortality, symptomatic heart failure, and hospitalization, plasma neurohormones were the only variables of predictive value. By stepwise regression analysis, plasma BNP was the only significant independent predictor of cardiovascular mortality (p = 0.001), whereas plasma ANP identified patients at risk of symptomatic heart failure and hospitalization (p = 0.002 and 0.019, respectively). This study indicates that plasma BNP measured after AMI is a powerful neurohormonal predictor of subsequent cardiovascular mortality, whereas plasma ANP correlates better with the development of symptomatic heart failure and hospitalization. Routine measurement of both of these peptides in the period immediately after an AMI may provide a simple means of risk stratification with different information gained from each peptide. (Am J Cardiol 1996;78:284–287)

Natriuretic effect of non-pressor doses of endothelin-1 in conscious dogs.

1. Renal, endocrine and haemodynamic responses to separate intravenous infusions of three doses of endothelin-1 (40, 400 and 4000 fmol kg-1 min-1) were investigated in conscious dogs. 2. Administration of 40, 400 and 4000 fmol kg-1 min-1 endothelin-1 for 120 min increased plasma endothelin-1 levels by two-, seven- and 250-fold, respectively. 3. The two low doses did not have measurable effects on mean arterial blood pressure and heart rate but tended to increase glomerular filtration rate. The high dose increased mean arterial blood pressure (MABP; from 104 +/- 4 to 138 +/- 4 mmHg, P < 0.05) and decreased heart rate (from 71 +/- 4 to 46 +/- 3 beats min-1, P < 0.05) as well as glomerular filtration rate (from 47 +/- 3 to 19 +/- 5 ml min-1, P < 0.05). 4. At rates of 40 and 400 fmol kg-1 min-1, endothelin-1 increased sodium excretion about five- and eightfold, respectively. Relative changes in fractional sodium excretion were very similar. The high dose was markedly antinatriuretic (reducing sodium excretion from 8.3 +/- 1.1 to 1.2 +/- 0.2 mumol min-1, P < 0.05). 5. Diuresis increased during the administration of the two lower doses, which did not change plasma atrial natriuretic peptide or vasopressin concentrations. Urine flow increased after termination of the infusion of the pressor dose despite elevated plasma vasopressin and subnormal glomerular filtration rate. 6. Infusion of endothelin-1 at 40 fmol kg-1 min-1 did not change the concentrations of angiotensin II and atrial natriuretic peptide in plasma. Infusion of 400 fmol kg-1 min-1 was associated with a decrease in plasma angiotensin II, while plasma atrial natriuretic peptide was unchanged. The high dose of endothelin-1 markedly increased plasma levels of both hormones. 7. It is concluded that endothelin-1 at low plasma concentrations increases sodium excretion while a higher pressor dose of endothelin-1 is antinatriuretic. However, increases in plasma endothelin-1 seem to elicit diuresis over a wide concentration range, although possibly by different mechanisms.

The heart communicates with the kidney exclusively through the guanylyl cyclase-A receptor: acute handling of sodium and water in response to volume expansion.

Disruption of guanylyl cyclase-A (GC-A) results in mice displaying an elevated blood pressure, which is not altered by high or low dietary salt. However, atrial natriuretic peptide (ANP), a proposed ligand for GC-A, has been suggested as critical for the maintenance of normal blood pressure during high salt intake. In this report, we show that infusion of ANP results in substantial natriuresis and diuresis in wild-type mice but fails to cause significant changes in sodium excretion or urine output in GC-A-deficient mice. ANP, therefore, appears to signal through GC-A in the kidney. Other natriuretic/diuretic factors could be released from the heart. Therefore, acute volume expansion was used as a means to cause release of granules from the atrium of the heart. That granule release occurred was confirmed by measurements of plasma ANP concentrations, which were markedly elevated in both wild-type and GC-A-null mice. After volume expansion, urine output as well as urinary sodium and cyclic GMP excretion increased rapidly and markedly in wild-type mice, but the rapid increases were abolished in GC-A-deficient animals. These results strongly suggest that natriuretic/diuretic factors released from the heart function exclusively through GC-A.

Comparison of renal function under deliberate hypotension during epidural plus light-enflurane anesthesia and during enflurane anesthesia.

We compared the effects of deliberate hypotension induced with trimethaphan on renal function and renal tubular damage under combined epidural and light-enflurane anesthesia (epidural group) and enflurane anesthesia alone (enflurane group). The mean arterial blood pressure was maintained at 50-55 mm Hg for 2.5 h in both groups using continuous infusion of trimethaphan. The urine volume and free water clearance were significantly greater in the epidural group than in the enflurane group [1.8±1.8 (SD)vs 0.4±0.3 ml·kg-1·h-1 and 0.81±1.30vs -0.15±0.22 ml·min-1, respectively] (P<0.05). The creatinine clearance and fractional sodium excretion rate did not differ significantly between the two groups. Urinary excretion of norepinephrine was significantly less in the epidural group than in the enflurane group (P<0.05); however, epinephrine excretion did not differ. Urinary excretion ofN-acetyl-β-D-glucosaminidase was significantly less in the epidural group than in the enflurane, group (4.2±2.5vs 12.2±4.6 U·g-1 CR) (P<0.01). The plasma antidiuretic hormone concentration was significantly lower in the epidural group compared to the enflurene group (13±23vs 57±42 pg·ml-1) (P<0.05). No significant difference in plasma atrial natriuretic peptide concentration was found between the groups. We conclude that renal function during trimethaphan-induced hypotension is better maintained under epidural plus light-enflurane anesthesia than under enflurane anesthesia alone.

Disturbance of peripheral microvascular fluid permeability by the onset of atrioventricular asynchrony in patients with programmable pacemakers.

In vitro and in vivo evidence suggests that atrial natriuretic peptide can enhance fluid flux from intravascular to extravascular compartments. The relevance of this to human pathophysiology remains unclear. To determine whether a central haemodynamic change associated with increased plasma concentrations of atrial natriuretic peptide produces detectable change in the capillary filtration coefficient in a peripheral microvascular bed. 12 patients with programmable dual chamber permanent pacemakers. Calf capillary filtration coefficient (using a modified plethysmographic technique) and plasma atrial natriuretic peptide concentrations were measured during atrioventricular synchronous and ventricular pacing. Atrioventricular asynchrony was associated with higher mean (SD) concentrations of atrial natriuretic peptide (231.9 (123.1) v 53.5 (38.8) pg/ml) and an increased mean (SD) calf capillary filtration coefficient (4.2 (1.1) v 3.6 (1.1) ml/min.mm Hg.100 ml x 10(-3)), but there was no correlation between the magnitude of the change in these variables in individual patients. The peripheral capillary filtration coefficient may change in response to altered central haemodynamics. Atrial natriuretic peptide remains one potential candidate mechanism, but other factors are also likely to be involved.