ANP Concentrations Research Articles

Amylin-induced suppression of ANP secretion through receptors for CGRP 1 and salmon calcitonin

Amylin cosecretes with insulin from pancreatic β-cells and shows high sequence homology with CGRP, adrenomedullin, and salmon calcitonin. This study aimed to investigate the effect of amylin on the atrial hemodynamics and ANP release from rat atria and to identify its receptor subtypes. Isolated perfused left atria from either control or streptozotocin-treated rats were paced at 1.3 Hz. The concentration of ANP was measured by radioimmunoassay and the translocation of ECF was measured by [ 3H]-inulin clearance. Rat amylin increased atrial contractility and suppressed the release of ANP. Rat CGRP showed similar effects but was approximately 300-fold more potent than amylin. Pretreatment with receptor antagonist for CGRP 1 [rat α-CGRP (8-37)] or salmon calcitonin [acetyl-(Asn 30, Tyr 32)-calcitonin(8-32), (AC 187)] blocked the suppressive effect of ANP release and the positive inotropic effect by rat amylin. However, receptor antagonists for amylin [amylin (8-37), acetyl-amylin] did not block those effects. Amylin (8-37), acetyl-amylin, or rat α-CGRP (8-37) alone accentuated the release of ANP with no changes in atrial contractility. The effect of rat amylin and rat amylin (8-37) on the ANP release was attenuated in streptozotocin-treated rats. We suggest that amylin suppressed ANP release with increased atrial contractility through receptors for CGRP 1 and salmon calcitonin and the attenuation of amylin and its antagonist on ANP release from streptozotocin-treated rat atria may be due to the downregulation of amylin receptor.

Pressão arterial e concentração plasmática do peptídeo atrial natriurético e do peptídeo natriurético tipo B, em gestações complicadas pela pré-eclâmpsia

OBJETIVO: o estudo busca determinar a existência de associação entre a elevação da pressão arterial e os níveis plasmáticos dos peptídeos natriuréticos ANP e BNP, na gestação complicada pela pré-eclâmpsia. MÉTODOS: em estudo transversal caso-controle, pareado por idade gestacional, 25 grávidas normotensas e 61 portadoras de pré-eclâmpsia foram avaliadas quanto ao nível da pressão arterial e às concentrações plasmáticas dos peptídeos natriuréticos ANP e BNP. Exames clínico e laboratoriais foram realizados para o diagnóstico de pré-eclâmpsia, sendo a pressão arterial medida de forma não invasiva. As dosagens hormonais foram obtidas por radioimunoensaio, após extração em colunas Sep-pak C18. Os valores médios das concentrações plasmáticas do ANP e BNP foram comparados entre grupos com pressão arterial progressivamente maiores. A correlação entre os valores da pressão arterial e os níveis plasmáticos do ANP e BNP no sangue materno foi também investigada pela de análise de regressão no grupo completo de gestantes e em grupos específicos excluindo-se a hipertensão anterior à gestação e, em seguida, excluindo-se aquelas sem hipertensão prévia. RESULTADOS: os valores plasmáticos de ANP foram 41.5±7.3, 78.4±13.1 e 89.2±13.4 pg/mL (p<0,00001) e os de BNP plasmático foram 79.5±15.8, 176.7±42.2 e 208.3±63.5 pg/mL (p=0,005), respectivamente, para os grupos de pressão arterial média =107 mmHg, 107-139 mmHg e =140 mmHg. Verificou-se correlação positiva entre as concentrações plasmáticas do ANP e os níveis pressóricos na pré-eclâmpsia, independente da existência de estado hipertensivo prévio à gestação (p<0,0001 para pré-eclâmpsia e p<0,01 para pré-eclampsia sobreposta à hipertensão arterial crônica), ao passo que as dosagens de BNP não se mostraram associadas à pressão arterial no grupo com hipertensão arterial prévia à gestação (p=0,004 para pré-eclâmpsia e p=0,18 para pré-eclampsia sobreposta à hipertensão arterial crônica). CONCLUSÃO: o agravamento da hipertensão na pré-eclâmpsia correlacionou-se com as concentrações séricas do ANP e BNP, embora os valores do BNP possam ser influenciados pela existência de estado hipertensivo prévio.

Influence of cardiopulmonary bypass (CPB) on the natriuretic peptides ANP and BNP. A comparison between long and short duration of CPB and off pump surgery

Plasma atrial and brain natriuretic peptide (ANP and BNP) are cardiac hormones secreted mainly due to cardiac overload. The study was designed to assess plasma concentrations of ANP and BNP in patients undergoing coronary bypass grafting (CABG) with long and short duration of cardiopulmonary bypass (CPB) and without CPB (off-pump surgery). We studied 45 patients scheduled for elective CABG. Patients were allocated in three groups: group A received CPB with a duration less than 60 minutes, group B more than 60 minutes and patients without CPB were allocated in group C. ANP and BNP were measured after induction of anaesthesia (T0), at the end of surgery (T1), 4 hrs. (T2), 24 hrs. (T3) and 120 hrs. postoperatively (T4). In all groups, ANP-levels increased from T0 to T4 (group A: from 3.7 +/- 2.1 to 8.9 +/- 8.0; group B: from 3.3 +/- 1.7 to 8.0 +/- 6.0; group C: from 3.0 +/- 1.6 to 5.3 +/- 2.3 pg/ml), but there were no significant differences between the groups. BNP-concentrations increased also from T0 to T4 (group A: from 34 +/- 18 to 234 +/- 164; group B: from 33 +/- 26 to 219 +/- 182; group C: from 33 +/- 24 to 77 +/- 55 pg/ml). Furthermore we measured significant higher BNP-levels in group B compared to group C at T3 and T4. No significant differences between group A and B were found. CPB influenced BNP, but not ANP plasma concentrations. An influence of the duration of CPB on ANP and BNP was not seen.

Body sodium and volume homeostasis.

maintenance of a “milieu interieur,” which allows our cells to function away from the ancient sea, is one of the most important functions of the body. Maintenance of constant extracellular osmolarity and sodium concentration depends on a precise balance between intake and excretion of sodium and

Effect of an ACE inhibitor and an AT1 receptor antagonist on cardiac hypertrophy.

The effect of long-term administration of delapril, an angiotensin converting enzyme inhibitor, and candesartan, an angiotensin II receptor blocker, on cardiac hypertrophy was investigated in spontaneously hypertensive rats (SHR). Delapril (2 mg/kg/ day) and candesartan (2 mg/kg/day) were administered for 5 weeks to 15-week-old male SHR. Echocardiographic estimation of cardiac morphology and function revealed cardiac hypertrophy in SHR compared with Wistar-Kyoto rats (WKY) which were used as normal controls. Both treated groups revealed regression of cardiac hypertrophy estimated by echocardiography. Heart to body weight ratio of treated SHR was also smaller than that of untreated SHR. Plasma BNP and ANP concentrations were increased in untreated SHR and decreased in the treated groups. Histological examination was performed using light microscopy and the area of fibrosis was estimated by computer. Reduction of the fibrotic area was observed in SHR treated with delapril and candesartan, although the latter was not statistically significant. Immunohistochemical examination using anti-collagen monoclonal antibody showed a decrease of type I collagen in treated SHR as compared with untreated SHR. It is concluded that both angiotensin converting enzyme inhibitor and angiotensin II receptor blocker sufficiently reduce blood pressure in SHR associated with regression of cardiac remodeling.

Effect of Natriuretic Peptides on in vitro Stimulated Adrenocorticotropic Hormone Release and Pro-Opiomelanocortin mRNA Expression by the Fetal Rat Pituitary Gland in Late Gestation

Objective and Methods: We investigated the effects of individual natriuretic peptides (atrial natriuretic peptide, ANP; brain natriuretic peptide, BNP, and C-type natriuretic peptide, CNP) on rat corticotropin-releasing factor stimulated adrenocorticotropic hormone (ACTH) secretion by the pituitary gland of 21-day-old rat fetuses in vitro and on pro-opiomelanocortin gene expression using in situ hybridization. Results: Graded concentrations of ANP, BNP, or CNP (10^–10, 10^–9, and 10^–8 mol/l) induced a log dose dependent inhibition of ACTH secretion induced by rat corticotropin-releasing factor (10^–10 mol/l). These natriuretic peptides showed equipotent effects on a molar basis. Moreover, ANP, BNP, or CNP at 10^–10 mol/l reduced significantly the pituitary pro-opiomelanocortin mRNA expression. In addition, the immunoreactive ANP, BNP, and CNP cells were localized in the anterior lobe, but not in the intermediate lobe of the fetal pituitary gland. Conclusions: These data suggest that the fetal pituitary gland may be both a source and a target for natriuretic peptides that might control ACTH synthesis and release via an endocrine and/or paracrine mechanism. The natriuretic peptides could participate, as well as glucocorticoids, in the control of the corticotropin-stimulating activity of the fetal rat in late gestation.

Anti-hypertensive effect of water extract of danshen on renovascular hypertension through inhibition of the renin angiotensin system.

A study was designed to elucidate the mechanism of anti-hypertensive effects of danshen in the two-kidney, one clip (2K1C) Goldblatt renovascular hypertensive model, which is the renin-angiotensin system (RAS)-dependent hypertensive model. We investigated the effects of water extracts of danshen on the angiotensin converting enzyme (ACE) activities, systolic blood pressure (SBP), and hormone levels in the plasma of 2K1C rats. ACE activity was inhibited by the addition of danshen extract in a dose-dependent manner. SBP was decreased significantly after administration of danshen extract in 2K1C, whereas plasma renin activity (PRA) was not changed. The plasma concentration of aldosterone (PAC) was decreased significantly in 2K1C group administered with Danshen extract, whereas the plasma concentration of ANP was increased by administration of danshen extract for three weeks. These results suggest that danshen has an anti-hypertensive effect through the inhibition of ACE, an essential regulatory enzyme of RAS.

Accentuation of ANP secretion to endothelin-1 in hypertrophied atria

To investigate modulation of ANP secretion by atrial hypertrophy, the secretion of ANP in response to stretch and endothelin-1 was studied using isolated perfused quiescent atria from rats treated with monocrotaline (MCT). Male Sprague-Dawley rats were given a single subcutaneous injection of 50 mg/kg MCT or saline and were sacrificed at 6 weeks. Rats with right heart hypertrophy showed an increase in ANP mRNA and decrease in tissue concentration of ANP in hypertrophied atria and a marked increase in plasma concentration of ANP. In isolated perfused hypertrophied right atria from MCT rats, changes in atrial volume induced by increased atrial pressure caused proportional increases in mechanically stimulated extracellular fluid (ECF) translocation and stretch-activated ANP secretion. Changes in atrial volume and mechanically stimulated ECF translocation in hypertrophied right atria were not different from those in control right atria. The stretch-activated ANP secretion was suppressed without significant difference in basal ANP secretion, as compared to control right atria. Therefore, the stretch-activated ANP secretion from hypertrophied right atria into the atrial lumen in relation to the ECF translocation (ANP concentration in the interstitium) was lower than that from control atria. A positive correlation between the stretch-activated ANP secretion in relation to the ECF translocation and tissue ANP content was found in control atria but not in hypertrophied atria. Endothelin-1 caused increases in stretch-activated ANP secretion in a dose-dependent manner, which were accentuated in hypertrophied right atria. Therefore, we suggest that atrial hypertrophy causes an attenuated response to stretch and accentuated response to endothelin-1 of ANP secretion.

The time course of natriuretic hormones as plasma markers of myocardial recovery in heart transplant candidates during ventricular assist device support reveals differences among device types

Background: The natriuretic hormones ANP and BNP are expressed differently in the myocardium. Both hormones have compensatory diuretic activity during heart failure. Mechanical stretch of the myocardial walls induces the expression of these hormones. In failing human myocardium, both ANP and BNP are transcribed in the ventricular myocardium in high amounts. We measured the plasma concentrations of ANP and BNP in patients supported by various ventricular assist devices (VADs) at various times. We analyzed the time courses of ANP and BNP to determine (1) the time scale of their down-regulation as a marker of putative myocardial recovery, (2) their steady-state levels under VAD support and (3) differences caused by various VAD devices. Methods: We analyzed ANP and BNP using commercially available radioimmune assays. We analyzed the time courses of patients supported by Thoratec® (THO) LVAD ( n = 8), TCI Heartmate® (TCI) ( n = 6), Novacor® (NOV) ( n = 7), and Lionheart® (LIO) ( n = 3). Results: Patients supported with NOV and some patients with TCI showed down-regulation of BNP to a steady-state level at 30 to 50 days, following a single exponential decay. In contrast, patients supported by THO or LIO did not reveal a determined time course of the natriuretic hormones. Only a few patients reached normal plasma values during VAD support. Conclusion: The time courses of ANP and BNP differ among VAD types because of construction and/or driving mode, which might be important when considering patients for weaning from VAD without heart transplant.

Measurement of plasma brain natriuretic peptide level as a guide for cardiac overload.

We examined whether measurement of the plasma BNP concentrations might be useful for the early diagnosis of the existence and severity of disease in patients with heart disease in daily clinical practice. The plasma BNP and ANP concentrations in 415 patients with heart disease and hypertension and 65 control subjects were measured. Patients with heart disease had higher plasma BNP and ANP concentrations than did those with hypertension or control subjects. Among the etiology of cardiac diseases, specifically dilated cardiomyopathy and hypertrophic cardiomyopathy, was associated with the highest plasma BNP concentrations, whereas dilated cardiomyopathy was associated with the highest plasma ANP concentrations. Plasma BNP concentrations showed an increase as the severity of the heart disease, as graded according to the NYHA classification of cardiac function, increased. In both patients with heart disease and hypertension, the plasma BNP values were higher in those who had abnormalities in their echocardiogram and electrocardiogram as compared to those without any abnormalities. The plasma BNP levels also showed a significant correlation with left ventricular wall thickness and left ventricular mass. On the other hand, the plasma ANP levels showed significant correlations with left ventricular dimension. Receiver operative characteristic analysis revealed that plasma BNP levels showed substantially high sensitivity and specificity to detect the existence of heart diseases. Measurements of the plasma BNP concentrations is useful to detect the existence of the diseases, and abnormalities of left ventricular function and hypertrophy in patients with heart disease in daily clinical practice.

Long-term treatment with neutral endopeptidase inhibitor improves cardiac function and reduces natriuretic peptides in rats with chronic heart failure.

Increased secretion of atrial and brain natriuretic peptide (ANP and BNP) from hearts is known to exhibit favorable effects in patients and animals with heart failure, and inhibition of neutral endopeptidase (NEP), an enzyme that degrades ANP and BNP, may further increase these peptide levels. However, it is still unknown whether such elevation of the ANP and BNP may offer a therapeutic benefit to the progression of chronic heart failure (CHF). We examined the effects of ONO-9902, a novel NEP inhibitor, on changes in hemodynamic parameters, NEP activity and neurohumoral factors in rats with CHF induced by left coronary artery ligation (CAL). Male Wistar rats (220-240 g) were subjected to induction of acute myocardial infarction by CAL. Rats were orally treated with ONO-9902 (300 mg/kg/day) from the 1st to 6th week after the operation. Hemodynamic and/or biochemical assessments were performed at the 1st and 6th weeks after the operation. A single administration of ONO-9902 inhibited the plasma and kidney NEP activities and thereby further augmented the elevation of plasma ANP concentration in rats with CAL at the 1st week after the operation. In rats with CAL at the 6th week after the operation, the left ventricular end-diastolic pressure (LVEDP) increased and cardiac output index (COI) decreased as compared with those of sham-operated rats. These changes were accompanied by marked increases in the plasma ANP, BNP and endothelin-1 (ET-1). Chronic treatment with ONO-9902 attenuated the increase in LVEDP and the decrease in COI. These changes were associated with a decrease in plasma ANP, BNP and ET-1 concentrations. The results suggest that chronic treatment with NEP inhibitor improves depressed cardiac function in rats with CHF. ONO-9902 may offer a new and possible therapeutic approach in patients with CHF.

Temporal changes in natriuretic and antinatriuretic systems after closure of a large arteriovenous fistula.

Surgical closure of a large arteriovenous (A-V) fistula in patients and animals is associated with prompt diuresis and natriuresis. However, the mechanisms underlying these changes remained largely unknown. The present study evaluated the hormonal balance between major antinatriuretic systems (plasma renin activity, PRA, and arginine vasopressin, AVP) and natriuretic systems (atrial natriuretic peptide, ANP, and renal nitric oxide, NO) in Wistar rats with an A-V fistula (1.2 mm O.D., side to side) between the abdominal aorta and inferior vena cava. The placement of an A-V fistula caused progressive sodium retention (UNaV decreased from 1500 to 100 microequiv./day), a significant drop in mean arterial blood pressure (MAP) from 127+/-3 to 75+/-2 mmHg (P<0.01), and a significant increase in ANP (from 94+/-12 to 389+/-135 pg/ml, P<0.05), PRA (from 22.1+/-2.0 to 47+/-14 ng angiotensin I [Ang I]/ml/h, P<0.05), AVP (from 14.2+/-3.6 to 37.7+/-9.6 pg/ml, P<0.05), norepinephrine (from 184.2+/-40.5 to 1112.6+/-293.2 pg/ml, P<0.05) and epinephrine (from 667.5+/-175.9 to 2049.8+/-496.9 pg/ml, P<0.05). Furthermore, these changes were associated with a 3-fold increase in the renal medullary immunoreactive levels of endothelial NO synthase (eNOS), an endogenous vasodilator that plays an important role in the regulation of medullary blood flow. After 6 days, rats with A-V fistula and maximal sodium retention underwent surgical closure of the A-V fistula. The A-V fistula closure was associated with dramatic natriuresis (UNaV=2563+/-78 and 1918+/-246 microEq/day on days 3 and 6 following the closure, respectively) and restoration of MAP to normal levels (111+/-6 mmHg); PRA decreased to 29+/-5 ng Ang I/ml/h, AVP to 20.3+/-7.1 pg/ml, and medullary eNOS declined to basal levels, whereas plasma ANP concentrations remained elevated (380+/-90 pg/ml) after 3 days and returned to normal (92+/-12 pg/ml) on day 6. These results demonstrate that the creation of A-V fistula is associated with activation of both natriuretic and antinatriuretic systems. Closure of A-V fistula is characterized by shifting the balance in favor of the natriuretic substances. Moreover, the observed alterations in medullary eNOS following the creation and closure of A-V fistula suggest that this system, an important determinant of medullary blood flow, may contribute significantly to the regulation of sodium excretion in this model.

Brain natriuretic peptide appears to act locally as an antifibrotic factor in the heart

In addition to cardiac myocyte hypertrophy, proliferation and increased extracellular matrix production of cardiac fibroblasts occur in response to cardiac overload. This remodeling of the cardiac interstitium is a major determinant of pathologic hypertrophy leading to ventricular dysfunction and heart failure. Atrial and brain natriuretic peptides (ANP and BNP) are cardiac hormones produced primarily by the atrium and ventricle, respectively. Plasma ANP and BNP concentrations are elevated in patients with hypertension, cardiac hypertrophy, and acute myocardial infarction, suggesting their pathophysiologic roles in these disorders. ANP and BNP exhibit diuretic, natriuretic, and vasodilatory activities via a guanylyl cyclase-coupled natriuretic peptide receptor subtype (guanylyl cyclase-A or GC-A). Here we report the generation of mice with targeted disruption of BNP (BNP-/- mice). We observed focal fibrotic lesions in ventricles from BNP-/- mice with a remarkable increase in ventricular mRNA expression of ANP, angiotensin converting enzyme (ACE), transforming growth factor (TGF)-beta3, and pro-alpha1(I) collagen [Col alpha1(I)], which are implicated in the generation and progression of ventricular fibrosis. Electron microscopic examination revealed supercontraction of sarcomeres and disorganized myofibrils in some ventricular myocytes from BNP-/- mice. No signs of cardiac hypertrophy and systemic hypertension were noted in BNP-/- mice. In response to acute cardiac pressure overload induced by aortic constriction, massive fibrotic lesions were found in all the BNP-/- mice examined, accompanied by further increase of mRNA expression of TGF-beta3 and Col alpha1(I). We postulate that BNP acts as a cardiocyte-derived antifibrotic factor in the ventricle.

Endothelin-1, endothelin-1 receptors and cardiac natriuretic peptides in failing human heart

Endothelin (ET)-1 is a potent vasoconstrictor peptide produced in the myocardium that can exert important effects on cardiac myocyte growth and phenotype; cardiac natriuretic peptides (ANP and BNP) are known to act as physiological antagonists of ET-1. In this study a comparative determination of ET-1 receptors and of the local productions of ET-1 and of ANP and BNP was made in different sites of failing and nonfailing hearts. Tissue from right and left atrium, right and left ventricle and interventricular septum from seven adult heart transplant recipients with end-stage idiopathic dilated cardiomyopathy (functional class III and IV, with ejection fraction < 35%) and from four post-mortem subjects without cardiac complications was analyzed. In failing hearts we observed a tendency to increase of density of binding sites, most evident in left ventricle (62.6 ± 22.6 fmol/mg protein vs. 29.0 ± 3.3, mean ± SEM, p = ns). A prevalence of ET-A subclass, observed in all samples, resulted more pronounced in failing hearts where this increase, found in all the cardiac regions, was more evident in left ventricle (p = 0.0007 vs nonfailing hearts). The local concentrations of ET-1, ANP and BNP resulted significantly increased in failing hearts with respect to controls in all sides of the heart. In failing hearts we have observed a tendency to increase in endothelin receptor density mainly due to a significant upregulation of ET-A subtype and a parallel increase of the tissue levels of ANP, BNP and ET-1 indicating an activation of these systems in heart failure.

Plasma and pericardial fluid natriuretic peptide levels in postinfarction ventricular dysfunction.

In the present study we examined plasma and pericardial fluid ANP and BNP concentrations in postinfarction ventricular dysfunction. The association of peptide levels to left ventricular (LV) dysfunction and to the localization of the myocardial infarction (MI) was studied. Plasma and pericardial fluid samples were obtained from 37 patients undergoing coronary bypass surgery. According to the ECG and preceding coronary angiography, the patients were divided into three groups: previous anterior myocardial infarction (MI) (n=12), previous inferior/posterior MI (n=15) and no history of MI (n=10). When compared to the control group with no MI, the patients with anterior MI had elevated plasma ANP and BNP (134+/-13 vs. 81+/-15 pg/ml, P<0.01 and 95+/-10 pg/ml vs. 26+/-8 pg/ml, P<0.01, respectively) and pericardial fluid BNP (473+/-60 pg/ml vs. 57+/-8 pg/ml, P<0.001) levels. The plasma natriuretic peptide concentrations were not increased in the patients with inferior/posterior MI, but the pericardial fluid BNP concentrations were greater than in the patients with no history of MI (129+/-35 pg/ml vs. 57+/-8 pg/ml, P<0.05). Six of the 12 patients with previous anterior MI had LVEF> or =45%. Despite their normal LV systolic function, these patients had increased plasma and pericardial fluid BNP levels when compared to the group with no history of MI (68+/-18 pg/ml vs. 26+/-8 pg/ml, P<0.05 and 534+/-258 pg/ml vs. 57+/-8 pg/ml, P<0.01, respectively). Previous anterior myocardial infarction was associated with increased cardiac BNP production even if the LV systolic function was normal (LVEF> or =45%). The high pericardial fluid BNP concentrations in postinfarction patients suggest that the BNP synthesis and release are augmented in the ventricular myocardium independent from the LVEF.

Opposite regulation of brain and C-type natriuretic peptides in the streptozotocin-diabetic cardiopathy.

C-type natriuretic peptide (CNP), a recent addition to the family of natriuretic peptides including atrial and brain natriuretic peptide (ANP, BNP), is believed to be an endothelium-derived vasodilator and to have an antimitotic effect. ANP and BNP concentrations are increased in conditions such as congestive heart failure, but cardiac CNP concentrations have not been investigated in this connection. Diabetes mellitus also involves myocardial dysfunctions without coronary artery disease or systemic hypertension. We therefore investigated the cardiac expression of CNP mRNA compared with that of BNP mRNA in streptozotocin (STZ)-diabetic rats. STZ- diabetic male Wistar rats (n=6) were studied in comparison with controls (n=6). The animals were characterised by their mean arterial blood pressure and plasma glucose concentrations. After extraction of total cardiac RNA, a specific cDNA probe of BNP was used for northern blot analysis, whereas myocardial CNP expression was analysed by an RNase-protection assay. Twelve weeks after diabetes was induced, the rats were normotensive (96.4+/-2.0 compared with 95.1+/-1.9 mmHg) and hyperglycaemic (615+/-61 compared with 165+/-21 mg/dl; P<0.001). Left ventricular pressure was significantly impaired (76.8+/-6.4 compared with 51.2+/-3.6 mmHg). STZ-diabetic rats had a 3.2-fold increase in cardiac BNP expression compared with controls. In contrast, cardiac CNP mRNA concentrations were decreased 2.6-fold. CNP seems to be downregulated like other peptides with antimitotic and vasodilator activities (nitric oxide, prostacyclin, kinins). This may contribute to cardiac dysfunction in diabetes mellitus and suggests that stimulation of CNP expression could provide cardiac protection in such cases.

Effects of natriuretic peptides on the gill vasculature of a hagfish, Eptatretus cirrhatus

An isolated, perfused gill pouch preparation and myography were used to determine responses of the branchial vasculature of a hagfish to the mammalian natriuretic peptides, rANP and CNP. In the isolated gill pouch preparation afferent perfusion pressures increased in the first 5 min of exposure to low concentrations (10 14 to 10 10 M) of ANP and CNP and then decreased below starting values by 15 min. At higher concentrations the depressor response prevailed and natriuretic peptides switched the flow away from the efferent artery to the venous route, which would fill the peribranchial sinus in vivo. At low concentrations ANP increased circumferential tensions in afferent branchial arterial rings. At higher concentrations afferent and efferent branchial arteries relaxed in response to ANP and CNP.

Plasma concentrations of atrial and brain natriuretic peptides and cyclic guanosine monophosphate in response to dobutamine infusion in patients with surgically repaired tetralogy of fallot.

We examined the plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP) and cyclic guanosine monophosphate (cGMP) during dobutamine infusion and their relationship with hemodynamic parameters in 14 patients with surgically repaired tetralogy of Fallot (TOF). Dobutamine was infused at an initial dose of 5 microgram/kg/min and increased by 5 microgram/kg/min up to 20 microgram/kg/min. The plasma ANP, BNP, and cGMP concentrations were determined before infusion, at the end of each stage, and 15 minutes after discontinuing dobutamine infusion. The plasma concentrations of ANP, BNP, and cGMP were elevated in all patients before dobutamine infusion. The ANP, BNP, and cGMP concentrations decreased in 11 of the 14 patients during dobutamine infusion. In contrast, the plasma ANP and BNP concentrations increased in the remaining 3 patients without a change in the cGMP concentration. The right ventricular pressure and volume were significantly elevated in these patients. The plasma cGMP concentration correlated with the ANP concentration (r = 0.62, p < 0.01) but not the BNP concentration. The plasma ANP concentration during dobutamine infusion correlated with right ventricular systolic pressure (r = 0.71, p < 0.05), mean right atrial pressure (r = 0.29, p < 0.05), and mean pulmonary capillary wedge pressure (r = 0.32, p < 0.05). The BNP concentration correlated with right ventricular volume (r = 0.61, p < 0.05) and systolic pressure (r = 0. 46, p < 0.05). In conclusion, rapid changes in ANP, BNP, and cGMP concentrations during dobutamine infusion reflect the changes in atrial and ventricle pressure and volume overload. In surgically repaired TOF, the ANP concentration is affected by right ventricular systolic pressure, right atrial pressure, and pulmonary capillary pressure. Furthermore, the BNP concentration reflects right ventricular pressure and volume overload.

Increased urinary atrial natriuretic peptide-like immunoreactivity excretion but decreased plasma atrial natriuretic peptide concentration in patients with hyperosmolar-hyperglycemic nonketotic syndrome.

This study was undertaken to measure urinary atrial natriuretic peptide-like immunoreactivity (ANP-LI) and plasma ANP concentration in patients with hyperosmolar-hyperglycemic nonketotic syndrome (HHNS) to investigate the change of renal ANP-LI and cardiac ANP synthesis in volume-depleted diabetic patients. The urine ANP-LI:creatinine ratio, plasma ANP level, and plasma renin activity (PRA) were measured in 12 patients with HHNS during the acute stage and after recovery, in 28 oral hypoglycemic agent (OHA)-treated type 2 diabetic patients, and in 23 normal subjects. ANP and PRA were measured by radioimmunoassay. These HHNS patients had severe hyperglycemia and hyperosmolality as well as increased blood urea nitrogen, creatinine, and PRA levels, as compared with normal subjects and OHA-treated type 2 diabetic patients. In these patients, the urinary ANP-LI:creatinine ratio (11.69 +/- 2.11 pmol/mmol) was significantly increased in comparison with the normal group (1.78 +/- 0.11 pmol/mmol) and OHA-treated diabetic patients (2.43 +/- 0.45 pmol/mmol), whereas plasma ANP concentration (5.12 +/- 0.72 pmol/l) was significantly lower than the corresponding values of the normal group (7.39 +/- 0.85 pmol/l) and OHA-treated diabetic patients (8.43 +/- 1.05 pmol/l). All of these abnormalities were significantly ameliorated after insulin, fluid, and electrolyte replacement. Our data show that urinary ANP-LI was significantly increased, whereas plasma ANP concentration was decreased, in the face of raised PRA in HHNS patients. This study indicates that renal ANP-LI substances and cardiac ANP may exhibit different responsiveness in diabetic patients with HHNS.

Renal urodilatin secretion is associated with diuresis and natriuresis after spontaneous, supraventricular tachycardia

Patients with paroxysmal supraventricular tachycardia (SVT) may have a polyuria after termination of tachycardia. There is increasing evidence that the renal peptide urodilatin (ANP (95-126))--and not plasma ANP (ANP (99-126))--is the member of the natriuretic peptide family mediating natriuresis and diuresis in man. In patients with SVT we, therefore, analyzed the relationship between diuresis, natriuresis, plasma ANP, urinary urodilatin excretion and renal excretion of cyclic GMP, the second messenger in the ANP system. During and after clinical presentation with spontaneously occurring SVT, two patients with AV-nodal and one patient with atrioventricular reentry tachycardia (heart rate 160 to 200 bpm) were studied. Urinary urodilatin excretion was correlated to diuresis (r = 0.73) and natriuresis (r = 0.93); similarly urinary cyclic GMP excretion was related to diuresis (r = 0.80) and natriuresis (r = 0.87; p < 0.001, respectively). In contrast, there was no significant correlation between plasma ANP concentrations and diuresis (r = 0.28, n.s.) or natriuresis (r = 0.11, n.s.). As an explorative analysis, stepwise multiple linear regression identified urinary urodilatin as the most important contributor to diuresis and natriuresis after SVT. These data on polyuria after spontaneous SVT further support the view that in man urodilatin is the member of the natriuretic peptide family participating in kidney physiology.