C-type natriuretic peptide levels in cor pulmonale and in congestive heart failure.

BACKGROUND--C-type natriuretic peptide (CNP) is a recent addition to the family of natriuretic peptides which includes atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Whilst the levels of ANP and BNP are increased in conditions such as congestive heart failure and cor pulmonale, abnormal levels of CNP in these conditions have not been reported. METHODS--Plasma levels of CNP were measured by specific radioimmunoassay in 12 young normal controls, 12 elderly normal controls, 12 patients with NYHA grade III-IV congestive heart failure, and in 16 patients with hypoxaemic cor pulmonale. RESULTS--Mean (SE) plasma levels of CNP were similar in young normal controls (0.46(0.03) pmol/l), elderly normal controls (0.43(0.05) pmol/l), and in patients with congestive heart failure (0.33(0.2) pmol/l). In patients with cor pulmonale, however, plasma levels of CNP were raised (1.39(0.27) pmol/l) 3.2-fold compared with age-matched controls. CONCLUSIONS--In cor pulmonale the increased plasma levels of CNP were not as great as the previously observed increases in levels of ANP (5.6-fold) or BNP (18.5-fold) in comparable patients. CNP may therefore be less important than ANP or BNP as a circulating counter-regulatory peptide in conditions of overactivity of the renin angiotensin system.     

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 microg/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 microg/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.     

Brain natriuretic peptide: role in cardiovascular and volume homeostasis

The identification of natriuretic peptides as key regulators of natriuresis and vasodilatation, and the appreciation that their secretion is under the control of cardiac hemodynamic and neurohumoral factors, has caused wide interest. The natriuretic peptides are structurally similar, but genetically distinct peptides that have diverse actions on cardiovascular, renal, and endocrine homeostasis. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are of myocardial cell origin, while cardiac natriuretic peptide (CNP) is of endothelial origin. ANP and BNP bind to the natriuretic peptide receptor (NPR-A) which, via 3' 5'-cyclic guanosine monophosphate (cGMP), mediates natriuresis, vasodialation, renin inhibition, and antimitogenic properties. CNP lacks natriuretic action but possesses vasodilating and growth inhibiting effects via the guanyl cyclase linked natriuretic peptide-B (NPR-B) receptor. All three peptides are cleared by natriuretic peptide-C receptor (NPR-C) and degraded by neutral endopeptidase, both of which are widely expressed in kidney, lung, and vascular wall. Recently, a fourth member of the natriuretic peptide, dendroaspsis natriuretic peptide (DNP) has been reported to be present in human plasma and atrial myocardium.     

Perioperative plasma concentrations of atrial and brain natriuretic peptides in patients undergoing hip arthroplasty

Acute hypotension, transient hypoxaemia and elevation of pulmonary artery pressure are well known to occur during cemented arthroplasty. The aim of this prospective clinical study was to characterize the relationship between plasma concentrations of atrial and brain natriuretic peptides (ANP, BNP), and changes in blood pressure in patients undergoing hip arthroplasty. Elevated ANP and BNP levels may be markers of inadequate myocardial reserve. We measured plasma ANP and BNP levels before the operation and 20 minutes after the cementing in 18 patients (54-90 yr). We defined a hypotensive response after cementing as a decrease in systolic blood pressure of more than 15 mm Hg below the pre-cementing value. In the hypotensive group, preoperative values of ANP were 123 +/- 48.5 pg/ml and BNP, 138 +/- 71.7 pg/ml. These values are significantly greater than those in the normotensive group (ANP 35.9 +/- 7.7, and BNP 17.2 +/- 3.2 pg/ml). High preoperative values of ANP and BNP are associated with more hypotension during cemented arthroplasty and could provide an indication of which patients are at risk of this complication.     

Renal actions of synthetic dendroaspis natriuretic peptide.

BACKGROUND: Dendroaspis natriuretic peptide (DNP), recently isolated from the venom of the green Mamba snake Dendroaspis angusticeps, is a 38 amino acid peptide containing a 17 amino acid disulfide ring structure similar to that of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). DNP-like immunoreactivity (DNP-LI) was reported to be present in human plasma and atrial myocardium and to be elevated in human congestive heart failure. Although previously named DNP, it remains unknown if DNP is natriuretic or if is it present in canine plasma, urine, and atrial myocardium. METHOD: Studies were performed in vivo in anesthetized dogs (N = 6) using intravenous infusion of synthetic DNP at 10 and 50 ng/kg/min. Employing a sensitive and specific radioimmunoassay for DNP, the presence of DNP-like peptide was assessed in the canine plasma and urine before, during, and following the administration of exogenous synthetic DNP. Additionally, we performed immunohistochemical studies using the indirect immunoperoxidase method with polyclonal DNP antiserum in normal atrial myocardium (N = 10). Atrial concentrations of DNP-LI were also assessed. RESULTS: We report that DNP is markedly natriuretic and diuretic, which, like ANP and BNP, is associated with the increase in urinary and plasma cGMP. DNP-like peptide is also detected in canine plasma, urine, and atrial myocardium. CONCLUSION: These studies establish that DNP is a potent natriuretic and diuretic peptide with tubular actions linked to cGMP and that DNP may play a physiological role in the regulation of sodium excretion.     

Hypertensive dysregulation and its modification by calcium channel blockade in nonoliguric renal failure

To investigate the pathogenetic constellation and its modification by calcium channel blockade in hypertension associated with chronic nonoliguric renal failure, blood pressure (BP), various pressor factors or correlates, cardiovascular responsiveness, and plasma atrial natriuretic peptide (ANP) were assessed in 15 hypertensive patients (serum creatinine 160-715 mumol/l) before and after 6 weeks of intervention with the agent nitrendipine. On placebo, these patients had a lower plasma angiotensin II (AngII) clearance and higher values of supine plasma AngII, aldosterone, norepinephrine (NE), and heart rate than healthy humans. Acute responses of BP to AngII and of heart rate to isoproterenol were blunted in the patients (p less than 0.05-0.001). Plasma ANP was elevated, correlated positively with systolic BP, and rose in response to NE pressor infusion (p less than 0.05-0.001). Exchangeable sodium and blood volume did not differ significantly from normal values. Nitrendipine reduced the cardiovascular responses to AngII, NE, and isoproterenol and lowered supine BP from 173/102 +/- 5/2 to 146/81 +/- 3/3 mm Hg and upright BP from 170/105 +/- 5/2 to 145/86 +/- 4/3 mm Hg (p less than 0.05-0.001); except for slightly increased plasma AngII, the levels of other endocrine variables, exchangeable sodium, blood volume, and creatinine clearance were not significantly modified. Conclusions: Hypertension accompanying chronic nonoliguric renal impairment seems to be strongly AngII and probably also NE dependent. Circulating ANP levels are high in this setting. Calcium channel blockade with nitrendipine effectively reduces cardiovascular AngII and NE dependence and BP.     

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.     

Improved neurohormonal markers of ventricular function after restoring sinus rhythm by the Maze procedure

BACKGROUND: Clinical results of the Maze procedure for treatment of atrial fibrillation (AF) are excellent, suggesting improved ventricular function after restoring sinus rhythm. However, long-term corresponding effects on the release of cardiac natriuretic peptides and other vasoactive hormones are incompletely investigated after isolated Maze surgery. METHODS: Plasma levels of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), antidiuretic hormone, aldosterone, and angiotensin II were measured in 15 patients (mean age, 52 +/- 11 years) undergoing isolated surgical Maze (III) procedures for medically refractory AF, preoperatively and 6 months postoperatively. At the time of blood sampling, hemodynamic correlates were obtained at baseline and after 6 and 12 minutes of rapid ventricular pacing at 150 stimulations/minute. RESULTS: All patients were free of AF at 6-month follow-up. The measured plasma levels of BNP, ANP, and angiotensin II were all significantly lower (p = 0.03) late after the isolated Maze procedure. Cardiac output was significantly higher postoperatively (p < 0.01). Other hemodynamic values and left atrial size were unchanged after surgery. Ventricular pacing caused almost identical hemodynamic changes in atrial pressures before and late after surgery, but the associated plasma ANP response was significantly attenuated postoperatively (p < 0.001). CONCLUSIONS: Levels of cardiac natriuretic peptides and angiotensin II as markers of ventricular function are improved in the long term after clinically successful isolated Maze procedures. ANP response to hemodynamic challenge by ventricular pacing was attenuated postoperatively, possibly due to atrial scarring.     

Atrial natriuretic peptide, brain natriuretic peptide and c-type natriuretic peptide: effects on testicular microcirculation and immunohistochemical localization

The effect of local injection of atrial (ANP), brain (BNP) and C-type (CNP) natriuretic peptides and an ANP antagonist (HS-142–1) on testicular microcirculation and vasomotion was studied using laser Doppler flowmetry. The natriuretic peptides were also localized immunohistochemically within the testis.
ANP, BNP-32, CNP-22 and CNP-53 all caused a dose-related increase in testicular blood flow. The effect of ANP was blocked by concomitant injection of the ANP antagonist. Immunoreactive (ir) CNP and ir BNP were found in Leydig cells whereas ir ANP was observed in the seminiferous tubules. It is suggested that the natriuretic peptides could play a role in local regulation of the testicular microcirculation.     

Renal effects of human atrial natriuretic peptide in patients after major vascular surgery

The effects were studied postoperatively of an infusion of atrial natriuretic peptide (ANP) 7.5 pMol–kg^-1 –min^-1 on renal function and haemodynamics in seven patients who had been operated with insertion of an abdominal aortic graft. Urine flow, glomerular filtration rate (GFR), renal plasma flow (RPF) and excretion of electrolytes and osmoles were measured for three periods of 20 minutes during infusion of ANP, in the morning of the day after surgery. Haemodynamic studies were conducted, and serum levels of ANP, catecholamines and plasma renin activity were measured.
ANP levels increased from 52 to approximately 250 pMol–L^-1 during ANP infusion and decreased after infusion to a level equal to baseline. GFR increased from 92 mL–min"¹ by 58, 20 and 21%, respectively. RPF was unchanged. Urine flow rate increased from 1.99 mL–min"' by 81, 151 and 173%, respectively. Fractional clearances of sodium, chloride and osmoles were increased during the second and third ANP periods whereas fractional potassium clearance did not change during the study. There were no changes in catecholamine levels or plasma renin activity during the study. Heart rate, mean arterial pressure and calculated systemic and pulmonary vascular resistance did not change whereas reductions occurred in cardiac index, mean pulmonary artery pressure, pulmonary artery wedge pressure and mean right atrial pressure. We conclude that infusion of ANP also in the postoperative situation increases GFR, diuresis and sodium excretion.     

Differential secretion of atrial and brain natriuretic peptide in critically ill patients

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones with natriuretic, vasorelaxant, and aldosterone-inhibiting properties. We analyzed the plasma of 178 critically ill patients for ANP, BNP, aldosterone, and serum sodium concentration, as well as serum and urine osmolality and sodium filtration fraction. Mean plasma concentrations of ANP and BNP were increased in critically ill patients compared with healthy controls (ANP, 14.3 +/- 5.8 pmol/L versus 8.8 +/- 3.2 pmol/L, P < 0.05; BNP, 26.2 +/- 10.7 pmol/L versus 4.6 +/- 2.8 pmol/L, P < 0.0001). The relative increases in ANP concentrations were comparable in all diseases. BNP concentrations, by contrast, showed a wider variation. The largest BNP concentrations were observed in patients who underwent cardiac surgical procedures and in patients with subarachnoid hemorrhage. ANP, but not BNP, was correlated with aldosterone levels (r = 0.4, P < 0.001), serum sodium (r = 0.42, P < 0.001), sodium filtration fraction (r = 0.3, P < 0.001), serum osmolality (r = 0.25, P < 0.01), urinary osmolality (r = -0.24, P < 0.01), and central venous pressure (r = 0.22, P < 0.01). ANP and BNP concentrations were increased in critically ill patients; however, this did not correlate with the severity of illness or mortality. Our data support a regulatory role for ANP in the maintenance of water and electrolyte balance. The physiologic role of BNP, by contrast, is less clear. ANP and BNP are not predictors for the severity of illness and mortality in critically ill patients.     

Haemodynamic effects of atrial natriuretic peptide in hypoxic chronic obstructive pulmonary disease.

BACKGROUND--Pulmonary artery pressure is elevated in patients with advanced chronic obstructive pulmonary disease (COPD). Release of atrial natriuretic peptide (ANP) is increased in pulmonary hypertension and this hormone may both selectively vasodilate pulmonary vessels and inhibit pulmonary vascular remodelling. The hypothesis that ANP has a physiological role in protection of the pulmonary circulation from pressure overload, and that it may be beneficial in patients with COPD, has been examined. METHODS--Ten patients with hypoxic COPD were infused for 30 minute periods with saline followed by ANP at 0.4, 2, and 10 pmol/kg/min respectively via a pulmonary artery catheter whilst monitoring haemodynamics and oxygenation. RESULTS--Levels of immunoreactive ANP (irANP) increased from a mean (SD) of 23 (15) pmol/l to a maximum of 94 (41) pmol/l. Neither systemic blood pressure, cardiac output nor total systemic vascular resistance showed any correlation with irANP levels. There were negative correlations between levels of ANP and mean pulmonary artery pressure which fell from 28.7 to 25.9 mm Hg, pulmonary artery wedge pressure which fell from 6.5 to 4.6 mmHg, and total pulmonary vascular resistance which fell from 489 to 428 dynes s cm-5. There was a small fall in PaCO2 from 6.2 to 5.9 kPa, whilst venous admixture and oxygen delivery both increased non-significantly. CONCLUSIONS--At these pathophysiological concentrations there was evidence that ANP selectively reduced right ventricular afterload. These data support the hypotheses that increased plasma levels of ANP may be beneficial in hypoxic COPD, and that endogenous ANP may ameliorate pulmonary hypertension in humans.     

Atrial natriuretic peptide in stable and decompensated chronic obstructive pulmonary disease.

BACKGROUND--Plasma levels of atrial natriuretic peptide (ANP) are elevated in patients with chronic obstructive pulmonary disease (COPD) and may have a role in preventing oedema formation in these patients. METHODS--Plasma ANP levels were measured in 60 patients with COPD and these measurements were related to pulmonary haemodynamics, response to treatment during exacerbations, and clinical patterns of the stable disease. RESULTS--Plasma ANP levels did not correlate significantly with right atrial or pulmonary arterial pressures but did correlate significantly with both the right ventricular end diastolic volume and right ventricular wall volume measured by magnetic resonance imaging. Oxygen (2 1/min by nasal prongs for 30 minutes) did not change the mean pulmonary arterial pressure or the level of plasma ANP. In 20 patients with an acute exacerbation of COPD plasma ANP levels were higher in those with oedema (302 (185) pg/ml) than in those without oedema (87 (43) pg/ml). Oxygen given for one hour had no effect on plasma levels of ANP. However, plasma ANP levels fell over the first three days during treatment in those with oedema, the fall correlating with the change in body weight. In a further 20 stable patients with hypoxic COPD, those with hypercapnia and previous episodes of oedema had higher levels of plasma ANP (120 (50) pg/ml) than normocapnic patients with no previous oedema (54 (15) pg/ml). CONCLUSIONS--The level of ANP is high in the plasma of patients with COPD, particularly during exacerbations in those with oedema. The association of a high plasma ANP level and volume overload is shown by the fall in ANP levels with treatment of the oedema, and the correlation between levels of ANP and right ventricular end diastolic or wall volumes.     

Effect of atrial natriuretic peptide on ischemic brain edema: changes in brain water and electrolytes

The effects of intraventricularly administered atrial natriuretic peptide (ANP) on the brain water, sodium, and potassium contents in ischemic brain edema were investigated. By use of a three-vessel occlusion model, ischemic brain edema was produced in the rat brain by 15 minutes of global ischemia followed by recirculation. Water content was measured by means of a drying/weighing method; sodium and potassium contents were measured by means of flame photometry. The effects of intraventricular administration of ANP were evaluated by a comparison between the groups given 2 and 5 micrograms of atriopeptin II (treated) and those given 0.9% NaCl (sham-treated). The treated groups showed significant decreases in brain water (P less than 0.02) and sodium (P less than 0.01) contents at 15 and 30 minutes after recirculation, whereas the brain potassium contents remained unaltered. Before ischemia and immediately after 15 minutes of ischemia, intraventricularly administered ANP did not significantly change the brain water, sodium, or potassium contents. There was no significant difference in the effect on the amount of brain water and sodium between the two doses (2 and 5 micrograms). These effects of ANP were thought not to be mediated by primary changes in serum osmolality and sodium and potassium concentrations, because intraventricular administration of ANP did not change them significantly. The present results reveal that, in ischemic brain edema, ANP may act directly on the central nervous system to inhibit brain water and sodium accumulation.     

Overexpression of brain natriuretic peptide in mice ameliorates immune-mediated renal injury.

One of major causes of end-stage renal disease is glomerulonephritis, the treatment of which remains difficult clinically. It has already been shown that transgenic mice that overexpress brain natriuretic peptide (BNP), with a potent vasorelaxing and natriuretic property, have ameliorated glomerular injury after subtotal nephrectomy. However, the role of natriuretic peptides in immune-mediated renal injury still remains unknown. Therefore, the effects of chronic excess of BNP on anti-glomerular basement membrane nephritis induced in BNP-transgenic mice (BNP-Tg) were investigated and the mechanisms how natriuretic peptides act on mesangial cells in vitro were explored. After induction of nephritis, severe albuminuria (approximately 21-fold above baseline), tissue damage, including mesangial expansion and cell proliferation, and functional deterioration developed in nontransgenic littermates. In contrast, BNP-Tg exhibited much milder albuminuria (approximately fourfold above baseline), observed only at the initial phase, and with markedly ameliorated histologic and functional changes. Up-regulation of transforming growth factor-beta (TGF-beta) and monocyte chemoattractant protein-1 (MCP-1), as well as increased phosphorylation of extracellular signal-regulated kinase (ERK), were also significantly inhibited in the kidney of BNP-Tg. In cultured mesangial cells, natriuretic peptides counteracted the effects of angiotensin II with regard to ERK phosphorylation and fibrotic action. Because angiotensin II has been shown to play a pivotal role in the progression of nephritis through induction of TGF-beta and MCP-1 that may be ERK-dependent, the protective effects of BNP are likely to be exerted, at least partly, by antagonizing the renin-angiotensin system locally. The present study opens a possibility of a novel therapeutic potential of natriuretic peptides for treating immune-mediated renal injury.     

Hemodynamic effects of infusions of alpha-human atrial natriuretic peptide in anesthetized dogs]

The purpose of this study is to investigate and compare the hemodynamic effects of infusion of alpha-human atrial natriuretic peptide (alpha-hANP) at three different doses. Mongrel dogs were anesthetized with 0.87% halothane in oxygen. alpha-hANP was infused for one hour with a constant rate at either 0.3, 1.0, or 10.0 micrograms.kg-1.min-1, respectively. They were randomly divided into four groups. Group A-1 received 0.3 micrograms.kg-1.min-1 of alpha-hANP; Group A-2 received 1.0 micrograms.kg-1.min-1 of alpha-hANP; Group A-3 received 10.0 micrograms.kg-1.min-1 of alpha-hANP; and Group C received normal saline as the vehicle and served as the control. Control values were obtained before infusion of alpha-hANP or vehicle was started, and hemodynamic variables were measured at 30 minutes intervals for two hours. Mean arterial pressure (MAP) of the group C showed no significant changes from control value. During and after infusion of alpha-hANP, MAP in the group A-2 and A-3 was significantly lower than the control values. The decrease in MAP of the group A-2 was the greatest. Heart rate decreased significantly at 60 minutes after termination of the infusion in all four groups. The reduction of cardiac index (CI) in the group-3 was the greatest. In the group A-3, it decreased for 31% from the control value at 60 minutes during infusion. However, this change was not significant. In contrast, the reduction in CI of the group A-2 was minimal. Mean pulmonary artery pressure (MPAP) of the group C showed no significant change from the control value. The patterns of changes in MPAP were similar to those of the alpha-hANP infused groups. It decreased progressively during the infusion. Systemic vascular resistance (SVR) was essentially unchanged in the group C. In the group A-2, SVR decreased slightly during the infusion period and then tended to increase after the infusion of alpha-hANP. In contrast, in the group A-1 and A-3, SVR increased progressively. The changes in left ventricular maximum dp/dt (LV dp/dt max) of the group C were minimal. The reduction in LV dp/dt max was more pronounced in group A-2 than in group A-3. In conclusion, our data show that hypotensive effects of alpha-hANP are associated with the reduction in cardiac output due to the decrease of cardiac contractility. However, the changes of hemodynamic variable are not dose-dependent.     

Effects of intraoperative administration of atrial natriuretic peptide

BACKGROUND: Biological activity of endogenous atrial natriuretic peptide (ANP) may decrease during cardiopulmonary bypass. To evaluate the effects of intraoperative administration of exogenous ANP in patients undergoing cardiopulmonary bypass, we conducted a prospective randomized study. METHODS: Eighteen patients undergoing mitral valve surgery were randomized to receive either ANP treatment (ANP group; n = 9) or no ANP treatment (control group; n = 9). Atrial natriuretic peptide was given immediately after initiation of cardiopulmonary bypass for 6 hours (0.05 microg x kg(-1) x min(-1)). Plasma ANP, brain natriuretic peptide and cyclic guanosine monophosphate (cGMP) levels, hemodynamic variables and renal function were assessed perioperatively. RESULTS: Administration of ANP increased plasma cyclic guanosine monophosphate levels, urine output and fractional sodium excretion, and decreased preload, afterload and plasma brain natriuretic peptide levels significantly (p < 0.05). Plasma cyclic guanosine monophosphate levels correlated with plasma ANP levels (r = 0.95, p = 0.0001), correlated with fractional sodium excretion (r = 0.53, p = 0.02), and correlated inversely with systemic vascular resistance (r = -0.54, p = 0.02). CONCLUSIONS: Intraoperative administration of ANP had potent effects on natriuresis and systemic vasodilation by elevating cyclic guanosine monophosphate levels. The results suggest that the technique is useful for the management of hemodynamics and water-sodium retention after cardiopulmonary bypass.     

The mature form of adrenomedullin correlates with brain natriuretic peptide in plasma of chronic hemodialysis patients

AIM: Adrenomedullin (AM), a hypotensive and natriuretic peptide, consists of an amidated mature form (mAM) and an intermediate form in human plasma, of which only mAM exerts biological activity. Like atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), plasma levels of mAM are reported to be significantly elevated in hemodialysis (HD) patients, suggesting that mAM may be stimulated partly by increased body fluid volume in a manner similar to the natriuretic peptides. Here, we examined the relationship between mAM levels and ANP or BNP levels and the effect of HD on plasma mAM in HD patients. PATIENTS AND METHODS: We measured plasma levels of mAM, total AM (tAM), ANP and BNP before and after HD in patients on long-term HD (n = 22, mean age 56.3 +/- 3.2 years) using radioimmunoassay. RESULTS: Baseline mAM (2.7 +/- 0.3 fmol/ml) and tAM (23.6 +/- 2.0 fmol/ml) were significantly higher in HD patients than in healthy subjects (1.1 +/- 0.2 fmol/ml, 9.0 +/- 2.1 fmol/ml, respectively). HD significantly reduced the levels to 1.2 +/- 0.2 fmol/ml and 13.8 +/- 1.4 fmol/ml, respectively, although tAM levels were still elevated compared to healthy subjects. Similar plasma ANP and BNP levels were obtained in HD patients. There were significant correlations between mAM and tAM levels before and after HD and between HD-induced changes in mAM and tAM levels. In the pre-HD state, levels of both mAM and tAM correlated significantly with BNP levels, but the correlation of BNP with mAM was closer than that with tAM. In contrast, no correlations were observed between the 2 forms of AM and ANP. Changes in mAM levels during HD also correlated significantly with BNP but not ANP levels, although the changes in tAM did not correlate with those of the 2 natriuretic peptides. CONCLUSION: Our results suggest that the secretion/metabolism of mAM may be regulated in a manner similar to that of BNP in HD patients.     

Atrial natriuretic peptide and verapamil can prevent gentamicin induced acute renal failure in the rat

Summary: Calcium channel blockers are able to improve renal function in acute renal failure (ARF) and natriuretic peptides can also exert beneficial effects. At present it is unknown whether administration of atrial natriuretic peptide (ANP) and a calcium channel blocker given before a toxic lesion can prevent gentamicin induced ARF. the mechanisms of action of natriuretic peptides and calcium channel blockers are different and, as yet, it has not been clarified if combined administration can augment the effects on renal function. After a basal period we investigated the effects of verapamil (VER, 0.66 mg/kg), ANP, (30 μg/kg) and a combination of both (identical doses as described individually). the drugs were given intravenously for a period of 40 min (infusion period) before gentamicin (15 mg/kg, i.v.) was administered for induction of ARF. Basal values for glomerular filtration rate (GFR, mL/min) were around 1.8 with no differences between the groups. At the end of the infusion period (before application of gentamicin) GFR was significantly elevated with VER + ANP (3.13 ± 0.51), ANP (2.70 ± 0.59) and VER (2.34 ± 0.47) compared to controls (saline, 1.7 ± 0.48). After application of gentamicin GFR significantly dropped in the control group (0.77 ± 0.21, 0.75 ± 0.19, respectively), indicating development of ARF. In contrast with VER + ANP, ANP and VER GFR could be maintained for 30 min (2.47 ± 0.39, 2.28 ± 0.33, 2.22 ± 0.43, respectively) and 130 min (2.11 ± 0.32, 1.86 ± 0.29, 2.11 ± 0.28, respectively) after gentamicin. Moreover ANP and VER revealed natriuretic activity and, due to their vasorelaxing potency, also influenced arterial blood pressure. We conclude that both VER and ANP are able to prevent early gentamicin induced ARF when given before the toxic lesion. Both drugs induce hyperfiltration while infused, in particular when administered in combination.