Emergências hipertensivas como manifestação clínica inicial de síndrome coronariana aguda / Hypertensive emergencies as the initial clinical manifestation of acute coronary syndrome

Relata-se uma série de três pacientes idosos, apresentando hipertensão arterial e coronariopatia crônica,assintomáticos e clinicamente controlados até o início das alterações tensionais súbitas que marcaram o início da evolução do evento coronariano. Foram realizados ECG, enzimas cardíacas seriadas, raios-X de tórax eecocardiograma, optando-se por cineangiocoronariografia. Em todos os pacientes observou-se ausência de estresse emocional/físico exorbitante ou perda da adesão ao tratamento, ausência de precordialgia, presença de lesões obstrutivas críticas, com presença de trombos em vasos de grande relevância anatômica e funcional (artéria culpada), com retorno à estabilização pressórica anterior após correção da isquemia por angioplastia coronariana.

Hipertensão pulmonar na insuficiência cardíaca / Pulmonary hypertension in heart failure

A Hipertensão Pulmonar (HP) na Insuficiência Cardíaca é uma comorbidade muito prevalente e intimamente associada à elevada morbidade e mortalidade. A HP está associada à disfunção ventricular esquerda e ocorre por alterações venosas (hipertensão passiva e venocapilar pulmonar) e arteriais, culminando no remodelamento arterial pulmonar e desenvolvimento da hipertensão fixa ou irreversível. Nestes pacientes, duas alterações neurohormonais principais estão presentes: redução da síntese e liberação de óxido nítrico e aumento da expressão e atividade da fosfodiesterase tipo 5. O manejo agudo de pacientes com hipertensão pulmonar, por exemplo, durante os testes de reatividade vascular pulmonar pré-transplante cardíaco, já está bem estabelecido, e conduzido com o uso de vasodilatadores, como nitratos, óxido nítrico e sildenafil. Entretanto, o tratamento crônico de pacientes com HP e insuficiência cardíaca ainda permanece indefinido. Até o momento, os estudos existentes não são capazes de determinar os benefícios do uso prolongado de sildenafil na redução da morbidade e mortalidade deste subgrupo de pacientes. Porém, dispõe-se de dados que demonstram que o sildenafil está associado à melhora dos níveis de hipertensão pulmonar, da capacidade física, da função cardíaca e dos índices de oxigenação venosa periférica. O sildenafil, apesar de não recomendado pelas diretrizes de insuficiência cardíaca, como parte do arsenal terapêutico da HP, apresenta fortes evidências de que seu uso agudo e crônico pode constituir em opções viáveis no tratamento convencional de pacientes com IC crônica e hipertensão pulmonar, como veremos neste artigo.

The role of endothelin pathway in modulation of airway reactivity to methacholine in C57Bl/6 and BALB/c mice.

Endothelin peptides have been shown to increase cholinergic neurotransmission in the airway. Genetic differences in airway responsiveness to methacholine where reported in mice. The present study compared the airway reactivity to methacholine in C57Bl/6 and BALB/c mice, the involvement of endothelin on this reactivity and endothelin levels in lung homogenates. Whole airway reactivity was analyzed by means of an isolated lung preparation where lungs were perfused through the trachea with warm gassed Krebs solution at 5 ml/min, and changes in perfusion pressure triggered by methacholine at increasing bolus doses (0.1-100 microg) were recorded. We found that the maximal airway response to methacholine was much greater in C57Bl/6 than in BALB/c (Emax 34+/-2 vs 12+/-1 cmH(2)O, respectively). Bosentan (mixed endothelin A/B receptor antagonist; 10 mg/kg, i.p., 30 min before sacrifice) reduced lung responsiveness to methacholine in C57Bl/6 (58% at EC50 level) but had no effect in BALB/c mouse strain. This effect seems to be mediated by the endothelin ET(A) receptor since it was significantly reduced by the selective endothelin ET(A) receptor antagonist, BQ 123. Immunoreactive endothelin levels were higher in C57Bl/6 than in BALB/c lungs (43+/-5 vs 19+/-5 pg/g of tissue). In conclusion, airway reactivity to methacholine and lung endothelins content varies markedly between C57Bl/6 and BALB/c strains. Endothelins upregulate lung responsiveness to methacholine only in C57Bl/6, an effect achieved through the endothelin ET(A) receptor.

Angiotensin II and endothelin in the renal cortex during the evolution of glycerol-induced acute tubular necrosis.

Hypertonic glycerol injection is one of the most frequently used models of experimental acute renal failure. Late structural changes such as interstitial fibrosis in the renal cortex and tubular atrophy have been detected after severe acute tubular necrosis (ATN). The aim of this study was to investigate the expression of angiotensin II (AII) and endothelin during the evolution of the ATN induced by glycerol and their relationships with the late structural changes observed in the kidneys. Forty-nine male Wistar rats were injected with a 50% glycerol solution, 8 mL/kg, divided into equal amounts, each administered into one hind leg, and 18 with 0.15 M NaCl solution. Blood and urine samples were collected 1, 5, 30, and 60 days after the injections to quantify sodium and creatinine; the animals were killed and the kidneys removed for histologic and immunohistochemical studies. The results of the immunohistochemical studies were scored according to the extent of staining in the cortical tubulointerstitium. Glycerol-injected rats presented a transitory increase in plasma creatinine levels and in fractional sodium excretion. The immunohistochemical studies showed increased AII and endothelin staining in the renal cortex from rats killed 5 days after glycerol injection (p<0.001) compared with control that persisted until day 60. The animals killed on days 30 and 60 also presented chronic lesions (fibrosis, tubular dilatation, and atrophy) in the renal cortex, despite the recovery of renal function. AII and endothelin may have contributed to the development of renal fibrosis in these rats.

Interstitial alterations in renal cortex in acute tubular necrosis (ATN) post-renal transplantation and in patients with ATN not related to renal transplant.

BACKGROUND: Abnormalities of renal function with long-term implications can persist after acute tubular necrosis (ATN), probably because of permanent loss of nephrons. Residual areas of fibrosis are also observed in the renal cortex post-ATN. In this study, we investigate the interstitial alterations post-ATN using histological and immunohistochemical methods. METHODS: We studied 11 patients with ATN of different etiologies and 19 patients with ATN post-renal transplantation. Eleven patients with ATN post-renal transplantation and one with ATN not related to renal transplantation were submitted to more than one biopsy because of delayed renal function recovery. The immunohistochemical studies were performed using alpha-smooth muscle-actin (alpha-SM-actin), endothelin, nuclear factor-kappaB (NF-kappaB), Jun-N-terminal kinase (p-JNK) and fibronectin antibodies. We also analyzed the urinary content of transforming growth factor-beta (TGF-beta) during the acute phase of ATN. RESULTS: The immunohistochemical studies showed increased alpha-SM-actin, fibronectin, endothelin, p-JNK and NF-kappaB staining in the tubulointerstitium area from the renal cortex of all patients when compared with controls (p < 0.001), and these increase persisted in the patients submitted to sequential biopsies. One of the patients with ATN without renal transplant and six patients with ATN post-renal transplant developed chronic renal failure. There was a significant increase of TGF-beta excretion in the urine of patients with acute renal failure (p < 0.01) compared with control. CONCLUSIONS: Our data show that the enhancement of renal TGF-beta production and the persistent increase of myofibroblasts, fibronectin, endothelin, p-JNK and NF-kappaB in renal cortex tubulointerstitium post-ATN may explain the impaired recovery of renal function observed in patients post-ATN frequently observed in patients with ATN post-renal transplant.

Association of endothelin with lung hemorrhage induced by immune complexes in rats.

The participation of endothelins (ETs) in a model of neutrophil-dependent lung injury induced by intrabronchial instillation of rabbit antibodies to ovalbumin followed by i.v. injection of the antigens (Arthus reaction) was investigated. Hemorrhagic lesions were evaluated by measuring the extravasations of hemoglobin in lung parenchyma. From 5 min to 24 h after the Arthus reaction (AR), endothelin (ir-ET) levels in bronchoalveolar lavage fluid (BALF) and in plasma were measured by radioimmunoassay. BALF levels of ir-ET were not different between control and AR animals for the first 90 min after the antigen challenge but increased from 2 to 24 h after induction of AR. ET levels in the plasma did not change from the respective controls over the same 24 h period. Increased ir-ET in BALF was not affected by pretreatment with L-NAME (30 mg/kg, i.v.). A PAF antagonist (BN52021; 5 and 10 mg/kg, i.v.) increased ET content in BALF and decreased the intensity of the AR. Thiorphan (2 mg/kg, i.v.) inhibited the AR-induced hemorrhagic lesions in lungs. An ET(A) receptor antagonist, BQ-123 (1 mg/kg, i.v.) potentiated, whereas the ET(B) antagonist, BQ-788 (1 mg/kg, i.v.) inhibited the lung hemorrhage. It is concluded that ETs are released during and play a role in the lung AR.

Endotelina y riñón / Endothelin and kidney

Se discute la fisiología - fisiopatología del endotelio, el cual representa un órgano endocrino dinámico que regula la actividad mitogénica, secretora y contractil de la pared vascular, incluyendo la renal así como su relación con diversas patologías incluyendo un nuevo tipo de mecanismo productor de hipertensión arterial y las posibilidades de usar bloqueadores de receptores de endotelina en diversas formas de tratamiento y disminuir la progresión de la enfermedad renal y vascular en general, así como su papel en el transplante de diversos órganos y el papel inducido por los inmunosupresores. No es de extrañar que el Premio Nobel de Medicina de 1998 haya sido otorgado a investigadores de fisiología de la endotelina y las nuevas opciones terapéuticas

Endotelina: datos preliminares sobre su concentración en embarazadas normales y con hipertensión arterial / Endothelin: preliminary data upon its concentration in women with normal pregnancy and preeclampsia

Recientemente se ha demostrado la existencia de un péptido con origen en el endotelio de los vasos sanguíneos que tiene propiedades vasoactivas, denominado endotelina. Por ser la hipertensión arterial asociada a embarazo, un padecimiento de etiología desconocida caracterizado por vasospasmo glomerular con alteraciones de la capacidad venosa, se decidió investigar los niveles plasmáticos de endotelina en pacientes con preeclampsia y embarazo normal en diferentes etapas de gestación, con objeto de reconocer diferencias en las concentraciones de este péptido (endotelina) que permitieran explicar la aparición de hipertensión. Endotelina sólo se encontró significativamente elevada en preeclámpticas a término. Es posible por tanto, que esta nueva sustancia tenga alguna participación en el síndrome toxémico.(au)