Plasma Atrial Natriuretic Peptide Concentrations Research Articles

Participation of the inducible nitric oxide synthase on atrial natriuretic peptide plasma concentration during endotoxemic shock

Atrial natriuretic peptide (ANP) is a hormone secreted in response to atrial or ventricular volume expansion and pressure overload, respectively. However, it has been found in studies with animals and patients an increase in ANP plasma concentration, during advanced septic shock, despite the fall in mean arterial pressure (MAP). Several studies support the hypothesis that NO may be involved in the regulation of ANP release. Since NO may have an effect on ANP release, we hypothesized that NO pathway may participate in the control of the ANP release induced by the endotoxemic shock. Thus, the purpose of the present study was to assess the effect of the intravenous (i.v.) and intracereboventricular (i.c.v.) administration of aminoguanidine, an iNOS blocker, on plasma ANP levels and MAP during experimental endotoxemic shock. Experiments were performed on adult male Wistar rats weighing 180–240 g. Rats were injected i.v. by bolus injection with 1.5 mg/kg of Lipopolysaccharide (LPS) or saline (0.5 mL) and were decapitated 2, 4 and 6 h after LPS injection for ANP determination by radioimmunoassay. In a separate set of experiments, rats received intravenous (i.v.) (100 mg/kg) or intracerebroventricular (i.c.v.) (250 μg in a final volume of 2 μL) injection of aminoguanidine (AG). Thirty minutes after the i.c.v. or i.v. injections, animals received LPS and were decapitated 2, 4 and 6 h later to determine plasma ANP concentration. In the two set of experiments MAP and heart rate (HR) were measured each 15 min for a period of 6 h using a polygraph. When animals were injected with LPS, a reduction ( p < 0.01) in MPA and an increase in HR occurred. A significant increase in plasma ANP concentration occurred, coinciding with the period of drop in blood pressure. We found a significant increase in plasma ANP concentration after AG plus LPS injection, when compared to the rats treated with LPS plus saline. Further, the administration of AG plus LPS attenuated the decrease in the MAP after LPS and attenuated the increase in the HR when compared to the rats treated with LPS plus saline. Our study suggests that inducible NOS pathway may activate an inhibitory control mechanism that attenuates ANP secretion, which is not regulated by the changes in blood pressure.

Plasma Big Endothelin‐1, Atrial Natriuretic Peptide, Aldosterone, and Norepinephrine Concentrations in Normal Doberman Pinschers and Doberman Pinschers with Dilated Cardiomyopathy

Background: Dilated Cardiomyopathy (DCM) results in progressive myocardial and circulatory dysfunction causing activation of a number of neurohormonal systems, including the endothelin (ET) system, which is only beginning to be described in clinical veterinary medicine. Measurement of these circulating neurohormones possesses potential utility in the diagnosis, staging, and assessment of prognosis in cardiac disease. Hypothesis: We hypothesized that plasma big ET‐1, norepinephrine (NE), aldosterone, and atrial natriuretic peptide (ANP) concentrations in normal Dobermans would differ from those in Dobermans with DCM, and that concentrations of these hormones would be associated with time to congestive heart failure (CHF) or death. Animals: Thirty client‐owned Dobermans (10 each of normal, occult DCM, and overt DCM) were included in the study. Methods: Dogs underwent an echocardiogram, ECG, and blood sample collection. Neurohormones were measured by high‐pressure liquid chromatography (NE) or commercial assays. Results: Dogs with occult DCM had significantly higher ANP concentrations compared with normal dogs (least squares means [95% confidence interval, CI]: occult female 53.7 pg/mL [40.2–71.7] versus normal female 31.6 pg/mL [24.8–40.3], P= .026; occult male 86.1 pg/mL [64.7–115] versus normal male 12.1 pg/mL [5.1–28.7], P= .011). Dogs with overt DCM had significantly higher concentrations of all neurohormones compared with the normal group. Furthermore, increasing big ET‐1 (risk ratio [RR] 2.7, CI 1.3–8.6, P= .01) and NE concentrations (RR 3.9, CI 1.1–18.1, P= .03) over 1 month were associated with a shorter survival time. Conclusions and Clinical Importance: High ANP concentrations can identify dogs with advanced occult DCM. Increasing big ET‐1 or NE concentrations over time can be useful predictors of poor prognosis.

Plasma Big Endothelin-1, Atrial Natriuretic Peptide, Aldosterone, and Norepinephrine Concentrations in Normal Doberman Pinschers and Doberman Pinschers with dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) results in progressive myocardial and circulatory dysfunction causing activation of a number of neurohormonal systems, including the endothelin (ET) system, which is only beginning to be described in clinical veterinary medicine. Measurement of these circulating neurohormones possesses potential utility in the diagnosis, staging, and assessment of prognosis in cardiac disease. We hypothesized that plasma big ET-1, norepinephrine (NE), aldosterone, and atrial natriuretic peptide (ANP) concentrations in normal Dobermans would differ from those in Dobermans with DCM, and that concentrations of these hormones would be associated with time to congestive heart failure (CHF) or death. Thirty client-owned Dobermans (10 each of normal, occult DCM, and overt DCM) were included in the study. Dogs underwent an echocardiogram, ECG, and blood sample collection. Neurohormones were measured by high-pressure liquid chromatography (NE) or commercial assays. Dogs with occult DCM had significantly higher ANP concentrations compared with normal dogs (least squares means [95% confidence interval, CI]: occult female 53.7 pg/mL [40.2-71.7] versus normal female 31.6 pg/mL [24.8-40.3], P = .026; occult male 86.1 pg/mL [64.7-115] versus normal male 12.1 pg/mL [5.1-28.7], P = .011). Dogs with overt DCM had significantly higher concentrations of all neurohormones compared with the normal group. Furthermore, increasing big ET-1 (risk ratio [RR] 2.7, CI 1.3-8.6, P = .01) and NE concentrations (RR 3.9, CI 1.1-18.1, P = .03) over 1 month were associated with a shorter survival time. High ANP concentrations can identify dogs with advanced occult DCM. Increasing big ET-1 or NE concentrations over time can be useful predictors of poor prognosis.

Prospective screening for occult cardiomyopathy in dogs by measurement of plasma atrial natriuretic peptide, B-type natriuretic peptide, and cardiac troponin-I concentrations

To evaluate the use of measuring plasma concentrations of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and cardiac troponin-I (cTnI) to detect dogs with occult dilated cardiomyopathy (DCM). 118 client-owned dogs. Dogs were prospectively examined by use of ECG; echocardiography; and evaluation of concentrations of ANP, BNP, and cTnI. Occult DCM was diagnosed by evaluation of echocardiographic left ventricular dimensions and detection of ventricular arrhythmias on ECG. Sensitivity and specificity of assays for measurement of plasma concentrations of ANP, BNP, and cTnI to detect dogs with occult DCM were determined. Occult DCM was diagnosed in 21 dogs. A concentration of > 6.21 pg/mL for BNP had a sensitivity of 95.2% and specificity of 61.9% for identifying dogs with occult DCM. In contrast, concentrations of ANP and cTnI had relatively low predictive values. Blood-based screening for occult DCM in dogs can be accomplished by use of a BNP assay. Additional studies should be performed to optimize this method of screening dogs to detect occult DCM.

Alterations in Atrial Natriuretic Peptide and Its Receptor Levels in Long‐Term, Streptozotocin‐Induced, Diabetes in Rats

Diabetes mellitus (DM) shows a markedly increased incidence of cardiovascular pathology that leads to hypertension, endothelial macro- and microangiopathy, diabetic nephropathy, and myocardial infarction. Atrial natriuretic peptide (ANP), is a 28 amino acid peptide hormone synthesized mainly by the heart atria and ventricles. It has potent diuretic and natriuretic properties. In this article the effect of long-term DM on blood plasma, kidney, and heart atrial and ventricular ANP concentrations were evaluated in streptozotocin (STZ)-induced 8-month diabetic and control rats by using radioimmunoassay (RIA). Moreover, ANP receptors in STZ-induced, 8-month diabetic rat kidneys were studied by receptor autoradiography. In addition, the expression of ANP concentrations in the kidney of diabetic and control rats was evaluated by means of immunohistochemistry. Body weight loss and increased blood glucose levels were used as indices of DM in the STZ-induced diabetic rats. Our results showed significantly higher ANP concentrations in diabetic plasma (P < 0.05), kidney (P < 0.01), heart atria (P < 0.05), and ventricles (P < 0.01) compared to controls. We also demonstrated a significant decrease in ANP receptors in the outer cortex (P < 0.05), juxtaglomerular medulla (P < 0.05), and papilla (P < 0.05) of 8-month diabetic rat kidneys compared to controls. The observed increase in ANP levels in plasma and kidney could play a role in the development of diabetic nephropathy: probably by reducing the levels of ANP receptors in diabetic kidney. Furthermore, the role of ANP in the STZ-induced diabetic heart merits additional study.

The value and evaluation of plasma BNP and ANP in diagnosis of heart failure

目的 探讨血浆脑钠素(BNP)、心钠素(ANP)浓度变化对心力衰竭的诊断价值.方法 分别采用酶联免疫法和放射免疫法检测75例心力衰竭患者(NYHAⅡ～Ⅳ级)和25名健康对照者的血浆BNP和ANP浓度,同时采用纽约心脏病学会(NYHA)标准对心功能分级和用超声心动图检查评定患者心功能.结果 心力衰竭组血浆BNP浓度为(1 794.1±724.5) ng/L、ANP浓度为(948.5 ± 520.7) ng/L,与正常对照组BNP(90.5±55.8) ng/L、ANP(121.7±71.1 ) ng/L比较差异有统计学意义(P＜0.01).BNP浓度心功能Ⅱ级为(552.9 ±339.6) ng/L、Ⅲ级(1 303.9±566.4 ) ng/L、Ⅳ级(3 625.5±1 069.2) ng/L,两两比较差异有统计学意义(P＜0.05);ANP浓度Ⅱ级为(518.8±376.3) ng/L、Ⅲ级(1 061.9±521.3) ng/L、ⅣV级(1 264.7±798.1) ng/L,Ⅱ级与Ⅲ级、Ⅳ级比较差异有统计学意义(P＜0.05),而Ⅲ级和Ⅳ级比较差异无统计学意义(P＞0.05).左心室射血分数LVEF＞40%的患者BNP为(1 096.7±656.6) ng/L、ANP为(931.6±320.9 ) ng/L,LVEF＜40%的患者BNP(2 659.4±743.5 ) ng/L、ANP(974.3±555.6 ) ng/L,两组患者血浆BNP浓度差异有统计学意义(P＜0.05);而ANP差异无统计学意义(P＞0.05).BNP和ANP在受试者工作特征(ROC)曲线下的面积分别为0.97和 0.85,两者曲线下面积差异有统计学意义(P＜0.01).结论 血浆BNP比ANP对心力衰竭患者的诊断具有更高的准确性,BNP与超声心动图反映的血流动力学状况指标LVEF及NYHA分级具有较好的相关性,可以作为心力衰竭分级的一个良好的诊断指标。

Anxiety modulation by the heart? Aerobic exercise and atrial natriuretic peptide

Exercise has an anxiolytic activity and it increases the concentrations of atrial natriuretic peptide (ANP). Because ANP has an anxiolytic activity, this hormone might contribute to the anxiolytic effects of aerobic exercise. Cholecystokinin-tetrapeptide (CCK-4)-induced panic attacks were studied in 10 healthy subjects after "quiet rest" or 30 min of aerobic exercise. Plasma ANP concentrations were measured before and after exercise or quiet rest using a commercial IRMA kit. Compared to quiet rest, CCK-4-induced anxiety was reduced and plasma ANP concentrations were increased by prior exercise. This anxiolytic activity of exercise was correlated with the increase in plasma ANP concentrations. Our results suggest that besides other mechanisms, ANP might be a physiologically relevant humoral link between the heart and anxiety-related behavior contributing to the acute anxiolytic effects of exercise.

Abnormal rhythmic oscillations of atrial natriuretic peptide and brain natriuretic peptide in chronic renal failure

Secretion of ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide) is pulsatile in healthy humans. However, the patterns of secretion of ANP and BNP have not been studied in chronic renal failure. The aim of the present study was to test the hypotheses that ANP and BNP are secreted in pulses in dialysis patients, and that pulsatile secretion is regulated by prostaglandins. Blood samples were drawn every 2 min through an intravenously inserted plastic needle over a period of 1-2 h in 13 dialysis patients and 13 healthy control subjects (Study 1), and in 15 healthy control subjects, who participated in a randomized placebo-controlled cross-over study after treatment with indomethacin and placebo (Study 2). Plasma concentrations of ANP and BNP were determined by RIAs, and the results were analysed for pulsatile behaviour by Fourier transformation. The results from Study 1 showed that the secretion of ANP and BNP was pulsatile in nine patients with chronic renal failure. The maximum amplitude was significantly higher in chronic renal failure compared with control subjects for both ANP and BNP (ANP, 4.3 compared with 0.7 pmol/l; BNP, 2.0 compared with 0.3 pmol/l; values are medians) and correlated positively with the mean plasma level of ANP (rho=0.900, P=0.001; n=9) and BNP (rho=0.983, P=0.000; n=9). The frequency was the same for patients and controls. The results from Study 2 demonstrated pulsatile secretion in all subjects, but both the amplitude and frequency were unaffected by indomethacin. The maximum amplitude correlated positively with the mean plasma level of ANP and BNP during both placebo and indomethacin treatment. It can be concluded that the secretion of ANP and BNP is pulsatile with abnormally high amplitude in chronic renal failure, that prostaglandins apparently are not involved in the secretion of these peptides in healthy subjects and that the high secretion rate in chronic renal failure results in higher ANP and BNP in plasma.

Atrial Natriuretic Peptide and Renal Haemodynamics in Newborn Calves

The study was aimed to provide information on the dynamics of changes in the concentration of ANP in blood plasma of calves during the first seven days of their life and to find any association between blood plasma ANP concentration and effective renal blood (ERBF) and plasma flow (ERPF) and glomerular filtration rate (GFR). The experiment was carried out on 10 clinically healthy Black and White calves during the first seven days of postnatal life. The concentration of atrial natriuretic peptide (ANP) in blood plasma was determined with radioimmunoassay. The kidney function was assessed by clearance methods, using para-aminohippuric acid and inulin. The blood plasma ANP concentration increased with age. On the first day the mean concentration of ANP was 5.72 ± 1.34 pmol/l, on the 7th day it was 14.34 ± 2.09 pmol/l. The ERBF and ERPF during the first week of life showed variations, mean ERBF ranging within 280.22 ± 10.30 ml/min/m2 (1st day) and 338.25 ± 13.72 ml/min/m2 (7th day) and ERPF ranging between 179.77 ± 8.27 ml/min/m2 (1st day) and 245.22 ± 9.86 ml/min/m2 (7th day). The mean GFR on the first day was 35.68 ± 2.10 ml/min/m2 and significantly (p &lt; 0.01) increased on the second day 49.97 ± 1.76 ml/min/m2, subsequently GFR remained on a stabile level average 51.06 ml/min/m2. The studies showed no correlations between plasma ANP concentration and ERPF (ERBF) and GFR. These data indicate that in calves during the first seven days of postnatal life endogenous ANP did not change the effective renal blood (plasma) flow and glomerular filtration rate.

Neutral Endopeptidase Null Mice Are Less Susceptible to High Altitude-Induced Pulmonary Vascular Leak

Hypoxia increases pulmonary vascular leak, which is regulated in part by neutral endopeptidase (NEP). NEP is a cell-surface metalloprotease that degrades several vasoactive peptides, including endothelin-1 (ET-1) and atrial natriuretic peptide (ANP). We therefore hypothesized that NEP attenuates high altitude-induced pulmonary vascular leak. Wild-type and NEP null mice were exposed to a simulated high altitude (HA) of 6,728 m (22,000 ft; P(B) = 328 mmHg) or remained at the relatively low altitude (LA) of 1,500 m (4,920 ft; P(B) = 640 mmHg) for 24 h. Plasma ANP and ET-1 concentrations, right ventricular pressure (P(RV)), and indexes of lung injury were recorded. At HA, lung wet weight-to-body weight increased in all animals, but was greatest in the NEP wild-type mice. Vascular leak, as measured by Evans blue dye, increased only in the NEP wild-type mice at HA. P(RV) increased in both genotypes at HA. Plasma ANP concentrations increased at HA in both genotypes, but plasma ET-1 concentrations were elevated only in the NEP null mice at HA. Correlations between lung wet weight-to-body weight versus P(RV) (r = 0.56; p = 0.0136) and ANP versus P(RV) (r = -0.54; p = 0.02) were noted. We conclude that NEP null mice exposed to HA have a greater rise in ANP versus ET-1 plasma concentration, decreased pulmonary vascular pressure, and reduced high altitude-induced pulmonary vascular leak.

Atrial natriuretic peptide stimulates lipid mobilization during repeated bouts of endurance exercise

Atrial natriuretic peptide (ANP) controls lipolysis in human adipocytes. Lipid mobilization is increased during repeated bouts of exercise, but the underlying mechanisms involved in this process have not yet been delineated. The relative involvement of catecholamine- and ANP-dependent pathways in the control of lipid mobilization during repeated bouts of exercise was thus investigated in subcutaneous adipose tissue (SCAT) by microdialysis. The study was performed in healthy males. Subjects performed two 45-min exercise bouts (E1 and E2) at 50% of their maximal oxygen uptake separated by a 60-min rest period. Extracellular glycerol concentration (EGC), reflecting SCAT lipolysis, was measured in a control probe perfused with Ringer solution and in two other probes perfused with either Ringer plus phentolamine (alpha(1/2)-AR antagonist) or Ringer plus both phentolamine and propranolol (beta-AR antagonist). Plasma epinephrine, plasma glycerol, and EGC were 1.7-, 1.6-, and 1.2-fold higher in E2 than in E1, respectively. Phentolamine potentiated exercise-induced EGC increase during E2 only. Propranolol reduced the lipolytic rate during both E1 and E2 compared with the probe with phentolamine. Plasma ANP concentration increased more during E2 than during E1 and was correlated with the increase in EGC in the probe containing phentolamine plus propranolol. The results suggest that ANP is involved in the control of lipolysis during exercise and that it contributes to stimulation of lipolysis during repeated bouts of exercise.

The role of natriuretic peptides in cardioprotection

Atrial natriuretic peptide (ANP) and brain (B-type) natriuretic peptide (BNP) are circulating hormones of cardiac origin that play an important role in the regulation of intravascular blood volume and vascular tone. The plasma concentrations of ANP and BNP are elevated in heart failure, and they are considered to compensate for heart failure because of their diuretic, natriuretic, and vasodilating actions and inhibitory effects on renin and aldosterone secretion. Evidence is also accumulating from recent work that ANP and BNP exert their cardioprotective functions not only as circulating hormones but also as local autocrine and/or paracrine factors. In studies using cultured neonatal myocytes and fibroblasts, exogenous administration of both ANP and ANP antagonists demonstrated that ANP has antihypertrophic and antifibrotic functions. Corroborating these in vitro results, mice lacking natriuretic receptor-A (NPR-A), the receptor for ANP and BNP, develop cardiac hypertrophy and fibrosis independent of their blood pressure. Recent studies also suggest that the intracardiac natriuretic peptides/cGMP system plays a counter-regulatory role against the intracardiac renin-angiotensin-aldosterone system and TGF-beta mediated pathway. In a clinical setting, human recombinant ANP and BNP may be used for a therapy of heart failure; however, further evaluation is required in the future.

Measurement of Pro-C-Type Natriuretic Peptide in Plasma

Accurate measurement of peptides derived from pro-C-type natriuretic peptide (proCNP) in human plasma has been difficult for several reasons. Low plasma concentrations necessitate high assay sensitivity. In addition, sufficient specificity can be difficult because of the close sequence homology of CNP with atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). Cross-reacting antibodies are particularly troublesome in heart failure patients, in whom plasma concentrations of ANP and BNP are increased. Plasma extraction before measurement has also been necessary to avoid protein interference (1)(2); however, extraction can reduce assay performance because of low and inconsistent peptide recovery. The aim of the present study was to develop an RIA for measurement of proCNP in human plasma. Plasma was extracted by a simple procedure before immunoanalysis with antibodies raised against a unique epitope in proCNP. The proCNP concentrations in venous plasma from healthy individuals and heart failure patients were assessed. Additionally, proCNP concentrations were measured in plasma selectively sampled from the coronary sinus in heart failure patients. Human proCNP 1–10 extended C-terminally with 4 alanyl and 1 tyrosyl residue was custom synthesized for tracer preparation and standards. ProCNP 1–10 extended C-terminally with 4 alanyl and 1 cystyl residue was used for directional carrier coupling (Cambridge Biochemical Research Ltd.). In addition, human proCNP 1–7, proCNP 2–7, and mouse proCNP 1–10 were synthesized for specificity testing. The purities and identities of all peptides were verified by amino acid analysis and reversed-phase HPLC. Antisera against the N-terminal sequence 1–10 of human proCNP were produced by use of 10 mg of proCNP 1–10-Ala-Ala-Ala-Ala-Cys coupled to 20 mg of bovine serum albumin (3). The rabbit immunization procedure used has been described previously(4). We iodinated 5 μg (2.1 nmol) of the tyrosine-extended fragment (proCNP 1–10-Ala-Ala-Ala-Ala-Tyr), using a mild chloramine-T method (5). The iodinated peptide was …

Continuous Intra- and Postoperative Thoracic Epidural Analgesia Attenuates Brain Natriuretic Peptide Release After Major Abdominal Surgery

We investigated whether blocking afferent nociceptive inputs by continuous intra- and postoperative thoracic epidural analgesia (TEA) would decrease plasma concentrations of brain natriuretic peptide (BNP) in patients who were at risk for, or had, coronary artery disease. Twenty-eight patients undergoing major abdominal surgery received either general anesthesia supplemented with a continuous thoracic epidural infusion of 1.25 mg/mL bupivacaine and 1 microg/mL sufentanil (n = 14; TEA) or general anesthesia followed by IV patient-controlled analgesia (n = 14; IV PCA). Visual analog scale pain scores, hemodynamics, plasma catecholamines, cardiac troponin T, atrial natriuretic peptide (ANP), and BNP were serially measured preoperatively, 90 min after skin incision, at arrival in the intensive care unit, and in the morning of the first, second, and third postoperative day. Dynamic visual analog scale scores were significantly less in the TEA group. TEA reduced the postoperative heart rate without affecting other hemodynamic variables. Plasma epinephrine increased perioperatively in both groups but was significantly lower in the TEA group. Baseline ANP and BNP concentrations were similar between groups (TEA 3.4 +/- 1.8 and 27.0 +/- 12.3 pg/mL; IV PCA 3.1 +/- 2.0 and 25.9 +/- 13.0 pg/mL, respectively). ANP and BNP increased perioperatively in both groups, with significantly lower postoperative BNP levels in TEA patients (TEA 92.1 +/- 31.9 pg/mL; IV PCA 161.2 +/- 44.7 pg/mL). No such difference was observed in plasma ANP concentrations. Plasma cardiac troponin T concentrations were within normal limits in both groups at all times. We conclude that continuous perioperative TEA using local anesthetics and opioids attenuated the release of BNP in patients undergoing major abdominal surgery who were at risk for, or had, coronary artery disease.

Atrial natriuretic peptide release associated with smoke inhalation and physiological responses to thermal injury in sheep

Markedly elevated levels of plasma atrial natriuretic peptide (ANP), which exhibit potent diuretic and vasoactive properties, has been well documented in patients with acute lung injury. We examined the physiological effects of additional smoke inhalation on plasma ANP concentrations in an ovine burn model. Seventeen sheep were instrumented to receive fluid and have physiological measurements taken. The burn group ( n = 8) received 40% body surface area third degree burn and the burn + smoke group ( n = 9) received the same burn plus 48 breaths of cotton smoke insufflation. The animals were resuscitated according to the Parkland formula with Ringer's lactate in the following 72 h period. Hemodynamic, oxygenation, fluid balance, and plasma ANP levels were serially determined. The effects of smoke inhalation manifested as deteriorated oxygenation, and increased fluid accumulation after a sustained initial shock period of more than 12 h. Plasma ANP levels in the burn + smoke group showed a biphasic elevation, whereas the burn group showed no appreciable changes throughout the whole experimental period. The initial increase in plasma ANP concentrations occurred immediately after injury (from 96 ± 10 at baseline to 136 ± 17 pg/mL at 3 h after injury); thereafter, it decreased towards baseline value, followed by a second increase in the post resuscitation period (183 ± 43 pg/mL at 72 h after injury). Decreased urine output and accentuated pulmonary vascular resistance in the combined injury group was observed between the two ANP level peaks, indicating that ANP release modified physiological responses to the burn + smoke injury

Kir6.2-deficient mice are susceptible to stimulated ANP secretion: K channel acts as a negative feedback mechanism?

While atrial natriuretic peptide (ANP) has been shown to be released mainly from cardiac muscle cells in response to atrial distension, the regulatory mechanisms of ANP secretion are still not fully understood. We sought to determine whether the ATP-sensitive K+ (K(ATP)) channel modulates the secretion of ANP, using mice with homozygous knockout of the Kir6.2 (a pore-forming subunit of cardiac K(ATP) channel) gene. K(ATP) channel currents were recorded from isolated mouse atrial cells with patch-clamp techniques. Plasma ANP concentrations in anesthetized mice and ANP content and secretion in isolated atrial preparations were determined by radioimmunoassay. Action potentials were recorded from the isolated atria. Exposure to 2,4-dinitrophenol (100 microM) evoked a glibenclamide-sensitive K(ATP) channel current in atrial cells from wild-type (WT) but not Kir6.2 knockout (Kir6.2 KO) mice. Although there were no significant differences in the basal plasma ANP levels between WT and Kir6.2 KO mice, volume expansion caused a significant elevation of plasma ANP concentration in Kir6.2 KO but not WT mice with accompanying hypotension. When isolated left atria were stretched, ANP secreted into the bath from Kir6.2 KO atria was significantly higher than that from WT atria. Furthermore, stretching the atria from WT but not Kir6.2 KO mice significantly shortened the action potential duration. A hypotonic stretch of the membrane induced the glibenclamide-sensitive K(ATP) channel current in atrial cells from WT but not Kir6.2 KO mice. Kir6.2 is essential for the function of K(ATP) channel in mouse atrial cells. Given that Kir6.2 KO mice are susceptible to stretch-induced secretion of ANP, our results suggest that K(ATP) channels may act as a negative feedback mechanism for the control of ANP secretion.

Neurohormonal activation in severe scorpion envenomation: correlation with hemodynamics and circulating toxin

We studied the effects of scorpion ( Androctonus australis hector) venom on hemodynamics and on the release of catecholamines, neuropeptide Y (NPY), endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) in dog model of severe scorpion envenomation. Nine mongrel anesthetized dogs were submitted to mechanical ventilation through intubation and were administered intravenously purified dried scorpion venom ( Androctonus autstralis) 0.05 mg/kg. Measurements including pulmonary artery catheter derived parameters, serum toxin levels and humoral variables were performed at baseline (before venom injection) and 5, 15, 30 and 60 min after venom injection. Humoral variables included: serum lactate, epinephrine (EP), norepinephrine (NE), NPY, ET-1 and ANP plasma concentrations. Scorpion venom caused rapid and transient increase of mean arterial pressure (MAP) and PAOP associated with a marked and sustained decline in cardiac output (−55% at 60 min; P < 0.001). Hemodynamic changes were associated with a rapid and significant increase of all measured hormones. The highest increase was for NE (28-fold) and EP (25-fold). MAP was closely correlated with NE and less significantly correlated with toxin levels. Similarly, significant correlation was observed between PAPO and ANP plasma levels. These findings support the implication of excessive catecholamines release in hemodynamic disturbances of severe SE and suggest that NPY and ET-1 could be involved in this process. Serum toxin does not appear to consistently contribute to these effects. Through its correlation with PAOP, ANP could be a reliable and useful marker of cardiac dysfunction in SE.

Natriuretic peptide response to dynamic exercise in patients with atrial fibrillation

Background In patients with atrial fibrillation (AF) information regarding exercise release of atrial natriuretic peptide (ANP) is sparse and data on plasma brain natriuretic peptide (BNP) response to exercise is lacking. The aim of this study was to investigate plasma ANP and BNP response to exercise in patients with permanent AF and to assess if the response was different from the response in healthy age- and sex-matched control subjects. Methods Plasma venous concentrations of ANP and BNP were determined at rest, at peak exercise and 30 min from the end of exercise in 38 patients with permanent AF and in 43 age- and sex-matched healthy control subjects. Results Plasma concentrations of ANP and BNP were significantly higher in AF patients compared with the healthy control group at rest, peak exercise and after 30 min of recovery ( p<0.0001). ANP and BNP increased significantly during exercise in both patients with AF and in the healthy control subjects ( p<0.05). The increase in plasma concentration of ANP and BNP during exercise was significantly higher in AF patients compared with healthy controls ( p=0.0002 for ANP; p<0.0001 for BNP). In the recovery period plasma BNP decreased significantly ( p<0.0001) where as the decrease in plasma ANP was insignificant ( p=0.4). Conclusions Patients with permanent AF have elevated levels of ANP and BNP at rest and exhibit much higher exercise release compared to healthy control subjects. This enhanced secretion of potent vasodilating and natriuretic agents may represent an important compensatory mechanism to improve exercise capacity in patients with AF.

Lipid Mobilization with Physiological Atrial Natriuretic Peptide Concentrations in Humans

Atrial natriuretic peptide (ANP) in pharmacological concentrations stimulates lipid mobilization in humans. The objective was to determine the hemodynamic and metabolic response to physiologically relevant ANP concentrations. The design was a human physiological study, conducted in 2004. The study was conducted at an academic research institute. Fourteen healthy normal-weight men (30 +/- 1.2 yr) participated in the study. Intravenous infusion of human ANP (h-ANP) was administered at rates of 6.25, 12.5, and 25 ng/kg.min. We studied local changes in blood flow and glucose and lipid metabolism of abdominal sc adipose tissue and femoral skeletal muscle by microdialysis. Overall changes in energy expenditure and substrate oxidation rates were monitored by indirect calorimetry. The increase in serum nonesterified fatty acids and glycerol concentrations were correlated with ANP plasma concentrations (r(2) = 0.86 and r(2) = 0.76, respectively). In adipose tissue, glycerol increased from 53 +/- 6 micromol/liter to 87+/-13 micromol/liter (P < 0.001). In femoral skeletal muscle, glycerol concentrations did not change, whereas lactate-to-pyruvate ratio decreased from 91 +/- 23 to 32 +/- 4 (P < 0.001). Indirect calorimetry indicated an increase in lipid oxidation (P < 0.05) concomitantly with a decrease in carbohydrate oxidation (P < 0.01), without changes in overall energy expenditure. ANP briskly stimulates lipid mobilization and oxidation at plasma concentrations that are encountered in conditions such as heart failure. Natriuretic-peptide induced lipid mobilization might contribute to cardiac cachexia. Drugs that interfere with the natriuretic peptide system should be evaluated for potential metabolic side effects.

Effects of atrial natriuretic peptide at a low dose on water and electrolyte metabolism during general anesthesia

Study objective To assess the hemodynamic, renal, and endocrine effects of small continuous doses of atrial natriuretic peptide (ANP) in patients anesthetized with sevoflurane for gastrectomy. Design Prospective randomized study. Setting Operating room and wards of a university hospital. Patients 20 ASA physical status I and II patients scheduled for gastrectomy. Intervention Atrial natriuretic peptide (0.05 μg/kg/min; ANP group, n = 10) or saline (control group, n = 10) was infused continuously for 2 hours beginning at the start of the operation. Measurements Plasma concentrations of ANP, brain natriuretic peptide, cortisol, angiotensin II, and aldosterone; plasma renin activity; serum and urinary sodium, potassium, and chloride; and urinar output. Main results The ANP group showed much greater urine volume and sodium, potassium, and chloride excretion than the control group, although the ANP group had a lower arterial blood pressure. The infusion did not affect surgery-induced increases in hormones. No patients experienced excessive hypotension, bradycardia, or other perioperative complications. Conclusions Continuous intravenous infusion of ANP at 0.05 μg/kg/min during gastrectomy was associated with greater water and electrolyte excretion unaccompanied by changes in potentially interacting hormones. Low-dose infusion may be particularly safe and useful for controlling water and electrolyte metabolism intraoperatively.