RESUMO
BACKGROUND: Although end-stage dilated cardiomyopathy (DCM) is characterized by defects in beta-adrenergic receptor (beta-AR) activity and increased endothelin-1 (ET-1), possible interactions between these 2 systems remain to be defined. Accordingly, the goal of this study was to determine the effects of ET receptor activation on beta-AR signaling through measurement of cyclic adenosine monophosphate (cAMP) in normal and DCM myocardium. METHODS AND RESULTS: Myocardial sarcolemmal preparations were prepared from normal human (n = 6), dilated cardiomyopathic (n = 10), and ischemic cardiomyopathic (ICM, n = 10) tissue. Basal cAMP production was measured in the presence of ET-1 alone (10(-6) to 0(-9) mol/L) as well as after (-)isoproterenol (10(-6) to 10(-2) mol/L) or forskolin (0.05 to 30.0 micromol/L) stimulation. beta-AR and ET receptor profiles were determined by radiolabeled ligand assays. ET-1 inhibited basal cAMP production in all preparations in a concentration-dependent manner. However, beta-AR-stimulated cAMP production by either isoproterenol or forskolin was not significantly affected by ET-1. beta-AR receptor density was reduced, and a selective reduction of the ET(B) receptor occurred in both forms of DCM. CONCLUSIONS: Under basal conditions, ET receptor stimulation reduced cAMP levels, which may influence contractility, particularly with DCM.
Assuntos
Cardiomiopatias/metabolismo , AMP Cíclico/biossíntese , Miocárdio/metabolismo , Receptores Adrenérgicos beta/metabolismo , Receptores de Endotelina/metabolismo , Adolescente , Adulto , Animais , Endotelina-1/metabolismo , Humanos , Técnicas In Vitro , Pessoa de Meia-Idade , Transdução de Sinais , SuínosRESUMO
BACKGROUND: Although reduced pulmonary clearance of endothelin-1 (ET-1) has been suggested to contribute to increased circulating levels in congestive heart failure (CHF), the regulation of the pulmonary ET system with CHF remains to be defined. Accordingly, the aim of the present study is to investigate the expression and activity of the ET system with the development of CHF. METHODS AND RESULTS: Pulmonary tissue samples were collected from pigs with pacing CHF (240 bpm, 3 wks, n = 10) and controls (n = 10). The pulmonary messenger RNA (mRNA) and protein levels of endothelin converting enzyme-1 (ECE-1) subisoforms, ET-1, and ET receptor profiles were determined. The gene expression of ET-1 precursor, ECE-1a, and ET(A) was upregulated 4-, 3-, and 2-fold, respectively, with CHF. Pulmonary tissue ET-1 was increased to 13 +/- 2 fmol/mg protein from control values of 5 +/- 1 fmol/mg protein (P <.05), and ECE-1 activity was augmented from 3,264 +/- 665 fmol/mg protein in control animals to 14,073 +/- 654 fmol/mg protein per hour in CHF animals (P <.05). The ET(B) receptor density decreased, whereas ET(A) receptors were increased in CHF, indicating a shift in the ET(A) to ET(B) ratio. CONCLUSIONS: Both the increased synthesis and the decreased clearance of ET-1 via ET(B) receptors may contribute to the increased systemic and pulmonary ET-1 levels in CHF.
Assuntos
Ácido Aspártico Endopeptidases/metabolismo , Endotelina-1/biossíntese , Insuficiência Cardíaca/metabolismo , Pulmão/metabolismo , Receptores de Endotelina/metabolismo , Animais , Enzimas Conversoras de Endotelina , Metaloendopeptidases , Modelos Animais , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/análise , Receptores de Endotelina/genética , SuínosRESUMO
Endothelin-1 (ET-1) is a peptide with potent vasopressor and mitogenic actions. Moreover, ET-1 displays modulatory effects on the endocrine system, including stimulation of angiotensin II and aldosterone production, and influences ion and fluid transport in the gut and kidney. A number of groups reported that ET-1 is overexpressed in the vasculature in several salt-sensitive models of experimental hypertension. African Americans present with a salt-sensitive and low-renin model of hypertension, and circulating plasma ET-1 levels are significantly increased in this population. The prevalence of hypertension and its complications is also higher in Blacks than in Whites and, despite extensive research, the reasons for this difference are not well understood. We propose that vasoactive, mitogenic, and renal effects of the ET system might contribute to the development, maintenance and/or complications of hypertension in African Americans.
Assuntos
Endotelina-1/fisiologia , Hipertensão/etnologia , Receptores de Endotelina/fisiologia , Negro ou Afro-Americano , Animais , Endotelina-1/sangue , Hemodinâmica , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Rim/irrigação sanguínea , Rim/fisiopatologia , Prevalência , Receptor de Endotelina B , Receptores de Endotelina/sangue , Cloreto de Sódio na Dieta , Estados Unidos , Sistema Vasomotor/fisiopatologiaRESUMO
Swine waste is commonly treated in the USA by flushing into an anaerobic lagoon and subsequently applying to land. This natural system type of application has been part of agricultural practice for many years. However, it is currently under scrutiny by regulators. An alternate natural system technology to treat swine wastewater may be constructed wetland. For this study we used four wetland cells (11 m width x 40 m length) with a marsh-pond-marsh design. The marsh sections were planted to cattail (Typha latifolia, L.) and bulrushes (Scirpus americanus). Two cells were loaded with 16 kg N ha(-1) day(-1) with a detention of 21 days. They removed 51% of the added N. Two additional cells were loaded with 32 kg ha(-1) day(-1) with 10.5 days detention. These cells removed only 37% of the added N. However, treatment operations included cold months in which treatment was much less efficient. Removal of N was moderately correlated with the temperature. During the warmer periods removal efficiencies were more consistent with the high removal rates reported for continuous marsh systems--often > than 70%. Phosphorus removal ranged from 30 to 45%. Aquatic macrophytes (plants and floating) assimilated about 320 and 35 kg ha(-1), respectively of N and P.
Assuntos
Ecossistema , Esterco , Nitrogênio/metabolismo , Fósforo/metabolismo , Eliminação de Resíduos Líquidos/métodos , Animais , Bactérias Anaeróbias/fisiologia , Arquitetura de Instituições de Saúde , Plantas , Suínos , TemperaturaRESUMO
BACKGROUND: Increased plasma levels of endothelin-1 (ET-1) occur with congestive heart failure (CHF), but the components of the enzymatic activation of ET-1 in the myocardium remain to be defined. Accordingly, endothelin converting enzyme-1 (ECE-1) activity and expression in normal and failing heart were examined. METHODS AND RESULTS: Left ventricular (LV) tissue samples were obtained from patients undergoing heart transplantation because of dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) and from normal donor hearts. The gene expression of ET-1 precursor and ECE-1a was upregulated 4- and 3-fold, respectively, in the failing heart. ECE-1 activity (fmol/mg protein per hour) was augmented from 2,291+/-257 in normal tissue samples to 5,507+/-666 in DCM samples and to 7,435+/-682 in ICM samples (P < .05). Phosphoramidon and a specific ECE-1 inhibitor, FR901533, inhibited ECE-1 activity by over 90%. However, inhibitors of neutral endopeptidase (thiorphan) and matrix metalloproteases (batimistat) did not affect the conversion of big ET-1 to ET-1. CONCLUSIONS: This study showed that the biosynthetic pathway of ET-1 is activated in LV myocardium in the failing heart, and the myocardial processing of big ET-1 is highly specific for ECE-1.
Assuntos
Ácido Aspártico Endopeptidases/análise , Ácido Aspártico Endopeptidases/metabolismo , Regulação da Expressão Gênica/fisiologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Fenilalanina/análogos & derivados , Regulação para Cima/fisiologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Cardiomiopatia Dilatada/complicações , Estudos de Casos e Controles , Enzimas Conversoras de Endotelina , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Ventrículos do Coração/patologia , Humanos , Metaloendopeptidases/antagonistas & inibidores , Fenilalanina/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tetraciclinas/farmacologia , Tiofenos/farmacologiaRESUMO
Modern biomedical instrumentation uses the technology that resulted from advances in electronics. Integrated circuit (IC) chips have replaced large systems of hard-wired electronic logic circuits and made them obsolete. Probably the most significant development in electronics is the IC chip called a microprocessor. Its capabilities make possible sophisticated instruments that can measure, compute, and display data for recurring physiological changes such as pulse rate. Because such instruments can function faster than the changes occur, information about the rate can be determined quickly, and remedial or corrective action can be implemented quickly in response to the data. This paper describes a pulse rate monitor that uses a microprocessor. It measures the occurrence rate of signals such as heart rate and respiration rate. It detects the signal rate, compares it with preset limits, and activates alarms as the limits are exceeded. The rate is measured and displayed at all times, until alarm conditions are detected. Then the display indicates the rate that caused the alarm condition. Upper and lower rate limits can be adjusted by the operator to suit the application.