Óxido nítrico e peptídeo atrial natriurético na predição de complicações da gestação

OBJETIVO: verificar a acurácia das dosagens séricas maternas do peptídeo atrial natriurético (ANP) e óxido nítrico (NO) para predição de complicações da gravidez. MÉTODOS: a casuística compreendeu 49 mulheres primigestas. As gestantes foram incluídas no estudo na 18ªsemana, momento em que foi coletada a amostra sangüínea para a realização das dosagens séricas. O ANP foi dosado pelo método de radioimunoensaio, utilizando kits Euro-dianostica (2000), considerando anormais valores superiores a 237,4 pg/mL (percentil 95). A dosagem do NO foi realizada pelo método de quimiluminescência, sendo considerados como anormais valores superiores a 17,8 µmol/L (percentil 95). Para análise estatística, utilizaram-se o teste t não pareado para a análise das variáveis quantitativas contínuas de distribuição normal; o teste de Mann-Whitney para amostras quantitativas não-paramétricas; o teste exato de Fisher na avaliação dos parâmentros qualitativos; e o teste de Pearson na avaliação das correlações. RESULTADOS: os dados não mostraram diferença significativa na concentração sérica do ANP, considerando o grupo que apresentou complicações gestacionais e/ou perinatais (média de 139,3±77,1 pg/mL) e o grupo controle (média de 119,6±47,0 pg/mlL), e nem na concentração sérica do NO, entre o grupo com complicações gestacionais e/ou perinatais (média de 11,1±4,6 µmol/L) e o grupo controle (média de 10,0±3,4 µmol/L). CONCLUSÕES: os resultados mostram que o ANP e o NO não foram bons indicadores de complicações da gestação.

Atrial natriuretic peptide and feeding activity patterns in rats

This review presents historical data about atrial natriuretic peptide (ANP) from its discovery as an atrial natriuretic factor (ANF) to its role as an atrial natriuretic hormone (ANH). As a hormone, ANP can interact with the hypothalamic-pituitary-adrenal axis (HPA-A) and is related to feeding activity patterns in the rat. Food restriction proved to be an interesting model to investigate this relationship. The role of ANP must be understood within a context of peripheral and central interactions involving different peptides and pathways

Release of plasma atrial natriuretic peptide after volume expansion is not related to pituitary-adrenal axis diurnal variation in normal subjects

The existence of a circadian rhythm of atrial natriuretic peptide (ANP) in humans is controversial. We studied the plasma ANP response to isotonic blood volume expansion in the morning and in the afternoon and its relationship with adrenocorticotropic hormone (ACTH)-cortisol diurnal variation in seven normal subjects. Basal plasma ANP level was similar in the morning (19.6 ± 2.4 pg/ml) and in the afternoon (21.8 ± 4.8 pg/ml). The ANP peak obtained with saline infusion (0.9% NaCl, 12 ml/kg) in the morning (49.4 ± 8 pg/ml) did not differ from that obtained in the afternoon (60.3 ± 10.1 pg/ml). There was no correlation between the individual mean cortisol and ACTH levels and the ANP peak obtained with saline infusion. These data indicate no diurnal variation in plasma ANP secretion induced by blood volume expansion and no relationship between plasma ANP peak and ACTH-cortisol diurnal variation

A liver metalloendopeptidase which degrades the circulating hypotensive peptide hormones bradykinin and atrial natriuretic peptide

A new metalloendopeptidase was purified to apparent homogeneity from a homogenate of normal human liver using successive steps of chromatography on DEAE-cellulose, hydroxyapatite and Sephacryl S-200. The purified enzyme hydrolyzed the Pro7-Phe8 bond of bradykinin and the Ser25-Tyr26 bond of atrial natriuretic peptide. No cleavage was produced in other peptide hormones such as vasopressin, oxytocin or Met- and Leu-enkephalin. This enzyme activity was inhibited by 1 mM divalent cation chelators such as EDTA, EGTA and o-phenanthroline and was insensitive to 1 µM phosphoramidon and captopril, specific inhibitors of neutral endopeptidase (EC 3.4.24.11) and angiotensin-converting enzyme (EC 3.4.15.1), respectively. With Mr 85 kDa, the enzyme exhibits optimal activity at pH 7.5. The high affinity of this endopeptidase for bradykinin (Km = 10 µM) and for atrial natriuretic peptide (Km = 5 µM) suggests that it may play a physiological role in the inactivation of these circulating hypotensive peptide hormones.

Relationship between the actions of atrial natriuretic peptide (ANP), guanylin and uroguanylin on the isolated kidney

Guanylin and uroguanylin are peptides that bind to and activate guanylate cyclase C and control salt and water transport in many epithelia in vertebrates, mimicking the action of several heat-stable bacteria enterotoxins. In the kidney, both of them have well-documented natriuretic and kaliuretic effects. Since atrial natriuretic peptide (ANP) also has a natriuretic effect mediated by cGMP, experiments were designed in the isolated perfused rat kidney to identify possible synergisms between ANP, guanylin and uroguanylin. Inulin was added to the perfusate and glomerular filtration rate (GFR) was determined at 10-min intervals. Sodium was also determined. Electrolyte dynamics were measured by the clearance formula. Guanylin (0.5 µg/ml, N = 12) or uroguanylin (0.5 µg/ml, N = 9) was added to the system after 30 min of perfusion with ANP (0.1 ng/ml). The data were compared at 30-min intervals to a control (N = 12) perfused with modified Krebs-Hanseleit solution and to experiments using guanylin and uroguanylin at the same dose (0.5 µg/ml). After previous introduction of ANP in the system, guanylin promoted a reduction in fractional sodium transport (%TNa+, P<0.05) (from 78.46 ± 0.86 to 64.62 ± 1.92, 120 min). In contrast, ANP blocked uroguanylin-induced increase in urine flow (from 0.21 ± 0.01 to 0.15 ± 0.007 ml g-1 min-1, 120 min, P<0.05) and the reduction in fractional sodium transport (from 72.04 ± 0.86 to 85.19 ± 1.48, %TNa+, at 120 min of perfusion, P<0.05). Thus, the synergism between ANP + guanylin and the antagonism between ANP + uroguanylin indicate the existence of different subtypes of receptors mediating the renal actions of guanylins.

Nitrergic modulation of vasopressin, oxytocin and atrial natriuretic peptide secretion in response to sodium intake and hypertonic blood volume expansion

The central nervous system plays an important role in the control of renal sodium excretion. We present here a brief review of physiologic regulation of hydromineral balance and discuss recent results from our laboratory that focus on the participation of nitrergic, vasopressinergic, and oxytocinergic systems in the regulation of water and sodium excretion under different salt intake and hypertonic blood volume expansion (BVE) conditions. High sodium intake induced a significant increase in nitric oxide synthase (NOS) activity in the medial basal hypothalamus and neural lobe, while a low sodium diet decreased NOS activity in the neural lobe, suggesting that central NOS is involved in the control of sodium balance. An increase in plasma concentrations in vasopressin (AVP), oxytocin (OT), atrial natriuretic peptide (ANP), and nitrate after hypertonic BVE was also demonstrated. The central inhibition of NOS by L-NAME caused a decrease in plasma AVP and no change in plasma OT or ANP levels after BVE. These data indicate that the increase in AVP release after hypertonic BVE depends on nitric oxide production. In contrast, the pattern of OT secretion was similar to that of ANP secretion, supporting the view that OT is a neuromodulator of ANP secretion during hypertonic BVE. Thus, neurohypophyseal hormones and ANP are secreted under hypertonic BVE in order to correct the changes induced in blood volume and osmolality, and the secretion of AVP in this particular situation depends on NOS activity.

Imidazoline receptors in the heart: a novel target and a novel mechanism of action that involves atrial natriuretic peptides

Chronic stimulation of sympathetic nervous activity contributes to the development and maintenance of hypertension, leading to left ventricular hypertrophy (LVH), arrhythmias and cardiac death. Moxonidine, an imidazoline antihypertensive compound that preferentially activates imidazoline receptors in brainstem rostroventrolateral medulla, suppresses sympathetic activation and reverses LVH. We have identified imidazoline receptors in the heart atria and ventricles, and shown that atrial I1-receptors are up-regulated in spontaneously hypertensive rats (SHR), and ventricular I1-receptors are up-regulated in hamster and human heart failure. Furthermore, cardiac I1-receptor binding decreased after chronic in vivo exposure to moxonidine. These studies implied that cardiac I1-receptors are involved in cardiovascular regulation. The presence of I1-receptors in the heart, the primary site of production of natriuretic peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), cardiac hormones implicated in blood pressure control and cardioprotection, led us to propose that ANP may be involved in the actions of moxonidine. In fact, acute iv administration of moxonidine (50 to 150 µg/rat) dose-dependently decreased blood pressure, stimulated diuresis and natriuresis and increased plasma ANP and its second messenger, cGMP. Chronic SHR treatment with moxonidine (0, 60 and 120 µg kg-1 h-1, sc for 4 weeks) dose-dependently decreased blood pressure, resulted in reversal of LVH and decreased ventricular interleukin 1ß concentration after 4 weeks of treatment. These effects were associated with a further increase in already elevated ANP and BNP synthesis and release (after 1 week), and normalization by 4 weeks. In conclusion, cardiac imidazoline receptors and natriuretic peptides may be involved in the acute and chronic effects of moxonidine.

Immunoperoxidase technique in experimental chronic chagasic myocarditis

Chagas'disease has been described as the commonest form of chronic myocarditis. An immunologic pathogenesis has been discribed for this form of the disease. So far, no immunoperoxidase technique has been used for the detection of immunological deposits in chronic experimental Chagas'myocardiopathy. Forty-one Swiss mice, three months old were inoculated intraperitoneally with doses between 10 and 10(5) Tulahuen trypomastigotes. Mice were reinoculated one month after with doses between 10² and 10(5) and sacrificed at 6 (n=21) and 9 months (n=9) after the first inoculation. ECGs were recorded before sacrifice. Immunoperoxidase technique (peroxidase-antiperoxidase method), immunofluorescence (direct and indirect) as well as histological studies were performed in myocardiums and skeletal muscles of the surviving animals. The most sensitive methods for detecting chronic chagasic infection were the routine histologic studies (73%) and the ECGs 83% and 89% on 6 and 9 mo. post-infected mice, respectively. Myocardial involvement varied from interstitial mild focal lymphocyte infiltrates up to replacement of myocytes by loose connective tissue. Atrial myocardiums (21/23, 91%) were more affected than ventricles (9/23, 39%). Typical chagasic nests were rarely found. Skeletal muscle involvement (11/18 and 7/9) varied from mild to extensive lymphocyte and plasmacell infiltrates, and necrotic fibers. The involved antigen were shown in skeletal muscles by the immunoperoxidase technique as diffusely arranged granular intracytoplasmatic deposit for both IgC and total immunoglobulins. The coincidence between this technique and histologic muscle lesions was 11/18 (61(%) in 6 mo. and 6/8 (75%) at 9 mo. post-infection. In heart, delicate granular deposits of total immunoglobulins were seen diffusely arranged within the ventricular myocytes; coincidence between immunoperoxidase technique anl histologic involvement increased from 36 to 66% in animals sacrifeced 6 and 9 mo. post-infection. This strongly stressed the increase of immunologic phenomena with the chronification of infection. Concerning sensitivity, immunoperoxidase and direct immunofluorescence were highly sensitive in skeletal muscle (100%, p < 0.01). Conversely, direct immunofluorescence technique showed poor results in heart while immunoperoxidase increased its sensitivity from 21.4% (at 6 mo.) to 66.6% (at 9 mo.) post-infection (p < 0.001). Considering the necessity of obtaining an adequate vaccine in order to prevent this disease an experimental model like this, rendering immunological reactions as revealed by the immunoperoxidase technique, would be useful.

Neuronal counting and parasympathetic dysfunction in the hearts of chronically Trypanosoma cruzi - infected rats

Ten male Wistar rats, chronically infected with Colombian, São Felipe (12SF) and Y strains of Trypanosoma cruzi and ten non-infected control animals were submitted to the bradycardia responsiveness test, an assessment of heart parasympathetic function, after phenylephrine injection. Six chagasic animals showed heart parasympathetic dysfuntion characterized by reduction in the index of bradycardia baroreflex responsiveness, as compared with the control group. Microscopic examination of the atrial heart ganglia of chagasic rats showed ganglionitis, but no statiscally significant reduction in the number of neurons.

Possible oral transmission of acute Chagas' disease in Brazil

In October, 1986, 7 to 22 days after a meeting at a farm in Paraíba state, 26 individuals presented with a febrile illness associated with bilateral eyelid and lower limb edema, mild hepatosplenomegaly, lymphadenopathy and, occasionally a skin rash. A 11-year-old boy exhibited atrial premature complexes and a 74-year-old patient developed acute heart failure. In two patients hospitalized in São Paulo city, acute Chagas' disease was diagnosed by the demonstration of circulating Trypanosoma cruzi. At autopsy in a fatal case, acute Chagas' cardiomyopathy was demonstrated. Xenodiagnosis were positive in 9 out of 14 tested patients. A specific IgG immune response was found in all patients and specific IgM antibodies were identified in 20 out of 22 tested patients. A epidemiological survey showed the existence of Triatoma brasiliensis in the outbuildings of this farm, but none in the house where most of the guests stayed. A high rate of infection with Trypanosoma cruzi was found in opossums. These observations together with those related to the food consumed by the patients, lead the authors to suggest that the human infections resulted from oral contamination probably originating from naturally infected marsupials in the area or crushed infected bugs.

Quantitative analysis of cardiac lesions in chronic canine chagasic cardiomyopathy

Lesions observed in chronic chagasic cardiopathy frequently produce electrocardiographic alterations and affect cardiac function. Through a computerized morphometrical analysis we quantified the areas occupied by cardiac muscle, connective and adipose tissues in the right atrium of dogs experimentally infected with Trypanosoma cruzi. All of the infected dogs showed chronic myocarditis with variable reduction levels of cardiac muscle, fibrosis and adipose tissue replacement. In the atrial myocardium of dogs infected with Be78 and Be62 cardiac muscle represented 34 and 50%, fibrosis 28 and 32% and adipose tissue 38 and 18%, respectively. The fibrosis observed was both diffuse and focal and mostly intrafascicular, either partially or completely interrupting the path of muscle bundles. Such histological alterations probably contributed to the appearance of electrocardiographic disturbances verified in 10 out 11 dogs which are also common in human chronic chagasic cardiopathy. Fibrosis was the most important microscopic occurrence found since it produces rearrangements of collagen fibers in relation to myocardiocytes which causes changes in anatomical physiognomy and mechanical behavior of the myocardium. These abnormalities can contribute to the appearance of cardiac malfunction, arrythmias and congestive cardiac insufficiency as observed in two of the analyzed dogs. Strain Be78 caused destruction of atrial cardiac muscle higher than that induced by strain Be62.

Fase aguda da doença de Chagas na Amazônia brasileira: estudo de 233 casos do Pará, Amapá e Maranhão observados entre 1988 e 2005

Foram estudados 233 casos de fase aguda da doença de Chagas, oriundos do Pará, Amapá e Maranhão, observados no período de 1988 a 2005, cento e sessenta deles retrospectivamente de 1988 a 2002 e setenta e três prospectivamente de 2003 a 2005. Entre os casos estudados 78,5% (183/233) faziam parte de surtos provavelmente por transmissão oral, acometendo em média 4 pessoas e 21,5% (50/233) eram casos isolados. Foram considerados casos agudos aqueles que apresentaram exames parasitológicos diretos (a fresco, gota espessa ou Quantitative Buffy Coat - QBC) e/ou IgM anti-Trypanosoma cruzi positivos. Foram feitos ainda xenodiagnósticos em 224 pacientes e hemoculturas em 213. Todos foram avaliados clinica e epidemiologicamente. As manifestações clínicas mais freqüentes foram febre (100%), cefaléia (92,3%), mialgia (84,1%), palidez (67%), dispnéia (58,4%), edema de membros inferiores (57,9%), edema de face (57,5%) dor abdominal (44,2%), miocardite (39,9%) e exantema (27%). O eletrocardiograma mostrou alterações de repolarização ventricular em 38,5% dos casos, baixa voltagem de QRS em 15,4% e desvio de SAQRS em 11,5%, extra-sístoles ventriculares em 5,8%, bradicardia em 5,8% e taquicardia em 5,8%, bloqueio de ramo direito em 4,8% e fibrilação atrial em 4,8%. A alteração mais freqüente vista no ecocardiograma foi o derrame pericárdico em 46,2% dos casos. Treze (5,6%) pacientes evoluíram para o óbito, 10 (76,9%) dos quais por comprometimento cardiovascular, dois por complicações de origem digestiva e um de causa mal definida.

Echocardiographic parameters associated with pulmonary congestion in outpatients with Chagas' cardiomyopathy and non-chagasic cardiomyopathy

INTRODUCTION: Despite significant left ventricular (LV) systolic dysfunction and cardiomegaly, pulmonary congestion does not seem to be a major finding in Chagas' cardiomyopathy (CC). This study sought to identify echocardiographic parameters associated with pulmonary congestion in CC and in dilated cardiomyopathy of other etiologies, such as non-CC (NCC), and to compare pulmonary venous hypertension between the two entities. METHODS: A total of 130 consecutive patients with CC and NCC, with similar echocardiographic characteristics, were assessed using Doppler echocardiography and chest radiography. Pulmonary venous vessel abnormalities were graded using a previously described pulmonary congestion score, and this score was compared with Doppler echocardiographic parameters. RESULTS: NCC patients were older than CC patients (62.4 ± 13.5 × 47.8 ± 11.2, p = 0.00), and there were more male subjects in the CC group (66.2% × 58.5%, p = 0.4). Pulmonary venous hypertension was present in 41 patients in the CC group (63.1%) and in 63 (96.9%) in the NCC group (p = 0.0), the mean lung congestion score being 3.2 ± 2.3 and 5.9 ± 2.6 (p = 0.0), respectively. On linear regression multivariate analysis, the E/e' ratio (β = 0.13; p = 0.0), LV diastolic diameter (β = 0.06; p = 0.06), left atrial diameter (β = 0.51; p = 0.08), and right ventricular (RV) end-diastolic diameter (β = 0.02; p = 0.48) were the variables that correlated with pulmonary congestion in both groups. CONCLUSIONS: Pulmonary congestion was less significant in patients with CC. The degree of LV of systolic and diastolic dysfunction and the RV diameter correlated with pulmonary congestion in both groups. The E/e' ratio was the hallmark of pulmonary congestion in both groups.

É a cardiomiopatia hipertrófica apical vista em uma amostra na cidade do Rio de Janeiro similar à encontrada no oriente?

OBJETIVO: Investigar a existência de diferença na forma de apresentação clínica e evolutiva da cardiomiopatia hipertrófica apical (CMHA), vista em uma amostra na cidade do Rio de Janeiro e a observada no oriente, onde foi descrita. MÉTODOS: Entre 156 pacientes com cardiomiopatia hipertrófica diagnosticados em nossa instituição, foram identificados 13 (8,34%) com a forma apical, sendo estudadas as suas manifestações clínicas, os meios de diagnóstico e a sua evolução. RESULTADOS: Eram 8 homens e 5 mulheres, com idades entre 19 a 75 anos, todos da raça branca, a maioria sintomática. O eletrocardiograma revelou ondas T gigantes em precordiais em 10 pacientes (76,92%), o ecocardiograma (ECO), a presença de hipertrofia apical em todos os casos, sendo em 10 (76,92%) restrita a ponta do ventrículo esquerdo (VE), em dois (15,4%) a ponta do ventrículo direito (VD) e, em 1 (7,68%), acometendo ambos os ventrículos. A cineventriculografia confirmou os achados do ECO. A evolução variou de 6 a 264 meses (x=95,4). Ocorreram dois óbitos (15,4%) em pacientes com o comprometimento associado ao VD, devido ao aumento significativo da dimensão dos átrios, ocorrência de fibrilação atrial, insuficiência valvar mitral e/ou tricúspide e tromboembolismo. Entre os vivos, a paciente com acometimento do VD evolui com restrição diastólica, e os restantes com lesão localizada do VE , 9 estão assintomáticos em uso de propranolol (8) ou amiodarona (1) e um permanece assintomático sem medicação. CONCLUSÃO: presentação, diagnóstico e evolução, porém notamos em 3 pacientes ( 23,08%) o acometimento da ponta do VD, não descrito no oriente, mas com péssimo prognóstico evolutivo.

Estudo mesoscópico da valva mitral e do seu anel fibroso

OBJETIVO: Estudar o arranjo espacial dos elementos fibrosos que constituem os folhetos da valva mitral e do seu anel fibroso. MÉTODOS: Foram utilizados 20 corações adultos, de ambos os sexos, fixados em formol a 10%. Isolaram-se a valva mitral, juntamente com o anel fibroso, e uma pequena quantidade de tecido muscular ao seu redor. Parte desse material foi incluído em parafina, submetido a cortes seriados de 40µm de espessura e corados pelo tricrômio de Azan e pela resorcina-fucsina, e o restante das peças dissecadas sob lupa estereoscópica, com ajuda de delicadas pinças e agulhas, para se observar a disposição dos feixes miocárdicos ao nível do anel mitral. RESULTADOS: Observou-se que o anel fibroso mitral era constituído por feixes colágenos de trajetória semicircular, envolvendo de forma incompleta o óstio atrioventricular, uma vez que era ausente na região ântero-medial do óstio. Verificou-se que os feixes miocárdicos ventriculares inseriam-se de forma oblíqua, na borda externa do anel, sendo que na região ântero-medial assumiam uma trajetória semicircular. Os folhetos da valva mitral eram constituídos de feixes colágenos dispostos, paralelamente, no sentido do maior eixo da válvula, recobertos pelo endocárdio atrial e ventricular. Os feixes colágenos, presentes na base dos folhetos valvares, praticamente se continuavam com os do anel fibroso. Observou-se, em alguns casos, a existência de delgados feixes miocárdios atriais no folheto valvar anterior, que praticamente eram restritos à região central das válvulas. CONCLUSÃO: Os folhetos da valva mitral e seu anel fibroso possuem uma continuidade estrutural, que demonstra que estes elementos funcionam de forma integrada no fechamento do óstio atrioventricular esquerdo durante a sístole ventricular, no que seria auxiliado pela redução do diâmetro do anel fibroso, através da contração dos feixes miocárdicos semicirculares que nele se inserem.