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1.
AJNR Am J Neuroradiol ; 43(10): 1424-1430, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36137656

RESUMO

BACKGROUND AND PURPOSE: The quality of leptomeningeal collaterals may influence the speed of infarct progression in acute stroke. Our main objective was to evaluate the association of leptomeningeal collateral score and its interaction with time with ischemic changes on CT in patients with acute stroke. MATERIALS AND METHODS: Adult patients with acute stroke symptoms and anterior circulation large-vessel occlusion on CTA from 2015 to 2019 were included. Routinely performed NCCT and multiphase CTA were reviewed to assess ASPECTS and the leptomeningeal collateral score. We built multivariate regression models to assess the association between leptomeningeal collateral score and its interaction with time and ASPECTS. Performance measures to predict poor ASPECTS at different time thresholds (identified with receiver operating characteristic curve analysis) were estimated in a subgroup of patients with poor leptomeningeal collateral scores. RESULTS: Leptomeningeal collateral scores 0-1 were associated with lower ASPECTS, and the model with dichotomized and trichotomized leptomeningeal collateral score showed a significant multiplicative interaction between time and the leptomeningeal collateral score. The negative predictive value for poor ASPECTS was >0.9 for at least the first 3 hours from stroke onset to imaging, and the positive predictive value was <0.5 for every time threshold tested in the subgroup of patients with leptomeningeal collateral scores 0-3. CONCLUSIONS: Poor (0-1) leptomeningeal collateral scores were associated with lower ASPECTS, and an increase in time has a multiplicative interaction with the leptomeningeal collateral score on ASPECTS.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Estudos Retrospectivos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/complicações , Angiografia Cerebral/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/complicações , Valor Preditivo dos Testes , Circulação Colateral , Angiografia por Tomografia Computadorizada
2.
Meat Sci ; 142: 1-4, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29630966

RESUMO

Pork bellies (n = 198) were scanned with dual energy X-ray absorptiometry (DXA). Visible and near-infrared reflectance (Vis-NIR) spectra were collected from the lean (latissimus dorsi), subcutaneous fat and intermuscular fat layers. Belly-flop angle and subjective belly scores were collected as measures of pork belly softness. Vis-NIR spectra from a single fat layer could explain between 72.7 and 81.1% of the variation in pork belly softness (43.6-72.4% in validation set). The combination of the lean and subcutaneous layers improved the calibration model fit to 79.7-99.9% (66.3-71.5% in validation set). The DXA estimates explained 62.3% of variation in pork belly softness (65.2% in validation set). Results indicated that DXA and NIR technologies could potentially be utilized for pork belly softness sorting in the pork industry.


Assuntos
Absorciometria de Fóton/métodos , Carne Vermelha/análise , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Animais , Feminino , Masculino , Gordura Subcutânea , Músculos Superficiais do Dorso , Sus scrofa
3.
Food Res Int ; 99(Pt 1): 660-669, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28784529

RESUMO

This study aimed to examine the influence of cooking methods and pre-determined refrigerated storage days on the production of lipid oxidation (TBARS), protein oxidation (PROTOX) and heterocyclic aromatic amines (HAA) in bacon. Forty-four pork bellies selected from pigs varying in breed, sex and diets to introduce variability in composition were processed as bacon. Sliced-bacon was stored at 4°C either for 2 or 28days and these storage groups were cooked either with microwave or frying pan. Microwave led to significantly higher PROTOX (P<0.001), while frying pan led to higher levels of HAA and TBARS in bacon (P<0.001). Frying pan cooking increased the saltiness and crispiness of bacon (P<0.05) whereas other sensory attributes were not affected (P>0.05) by the cooking methods and storage times. Similarly, the fatty acid composition of pork belly did not significantly influence the production of HAA, TBARS and PROTOX produced in bacon during cooking. Overall, microwave cooking had lesser impact on the production of carcinogenic compounds in bacon with only minor impact on sensory attributes.


Assuntos
Aminas/química , Culinária/métodos , Qualidade dos Alimentos , Armazenamento de Alimentos/métodos , Lipídeos/química , Proteínas de Carne/química , Animais , Cromatografia Líquida de Alta Pressão , Temperatura Alta , Humanos , Metabolismo dos Lipídeos , Micro-Ondas , Oxirredução , Carne Vermelha , Suínos , Fatores de Tempo
4.
Meat Sci ; 129: 54-61, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28254695

RESUMO

We explored various dimensional and compositional factors that can influence the perception of pork belly firmness. Bellies from 198 pigs of three different genotypes, two sexes, two slaughter weights and three different diets were recovered and belly firmness was assessed using the belly-flop angle and a 5-point scale subjective measurement. Dimensional and compositional factors were recorded on intact and sheet-ribbed bellies. Subjective belly score was negatively correlated with belly-flop angle (r=-0.89). Regression analysis accounted for 77 and 83% of the variability in subjective belly firmness and belly-flop angle measurement, respectively. Belly length, weight and width influenced both measures of belly firmness, but these effects were more important for the belly-flop angle. After correcting flop angle using belly length, the effect of belly weight disappeared and the effect of other traits was more like those observed for subjective scoring. Hence, undue effect of belly length should be corrected for if this set-up is to be implemented in commercial plants.


Assuntos
Carne Vermelha/normas , Ração Animal/análise , Animais , Peso Corporal , Dieta/veterinária , Feminino , Masculino , Controle de Qualidade , Fatores Sexuais , Sus scrofa/genética
5.
Meat Sci ; 121: 310-316, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27395824

RESUMO

The accuracy of dual energy X-ray absorptiometry (DXA) in assessing carcass composition from pigs with diverse characteristics was examined in the present study. A total of 648 pigs from three different sire breeds, two sexes, two slaughter weights and three different diets were employed. DXA estimations were used to predict the dissected/chemical yield for lean and fat of carcass sides and primal cuts. The accuracy of the predictions was assessed based on coefficient of determination (R(2)) and residual standard deviation (RSD). The linear relationships for dissected fat and lean for all the primal cuts and carcass sides were high (R(2)>0.94, P<0.01), with low RSD (<1.9%). Relationships between DXA and chemical fat and lean of pork bellies were also high (R(2)>0.94, P<0.01), with RSD <2.9%. These linear relationships remained high over the full range of variation in the pig population, except for sire breed, where the coefficient of determination decreased when carcasses were classified based on this variable.


Assuntos
Absorciometria de Fóton , Músculo Esquelético/química , Carne Vermelha/análise , Tecido Adiposo/química , Animais , Composição Corporal , Cruzamento , Dieta/veterinária , Feminino , Masculino , Suínos
6.
Talanta ; 119: 385-95, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24401429

RESUMO

Having acquired near infrared (NIR) hyperspectral images of intact pork loin samples through an NIR hyperspectral imaging system, the efficiency of a variety of image processing techniques including texture pattern analysis techniques were applied to process hyperspectral images so as to determine the intramuscular fat (IMF) content non-destructively. After the segmentation of region of interest (ROI), the raw spectral, texture-based spectral and textural characteristics of pork images were extracted by spectral averaging and pattern recognition techniques namely Gabor filter and improved gray level co-occurrence matrix (GLCM), respectively. First derivatives of the non-filtered and the Gabor filtered spectra were also investigated. Full waveband partial least squares regression (PLSR) was employed to determine the optimal parameters of Gabor filter and GLCM, and to select optimal wavelengths for IMF prediction. A stepwise procedure was applied to the optimal wavelengths to further optimize them to key wavelengths. Multiple linear regression (MLR) models were built based on the key wavelengths. Mean spectra and the Gabor filtered spectra outperformed GLCM. The best result, represented by correlation coefficients of calibration (Rc), cross validation (Rcv) and prediction (Rp) of 0.89, 0.89, and 0.86, respectively, was achieved using the first derivative of Gabor filtered spectra at 1193 and 1217 nm. To visualize the IMF content in pork, the distribution maps of IMF content in pork were drawn using a mean spectra-based MLR model. These promising results highlight the great potential of NIR hyperspectral imaging for non-destructive prediction of IMF content of intact pork.


Assuntos
Gorduras/análise , Produtos da Carne/análise , Músculo Esquelético/química , Animais , Análise Multivariada , Espectroscopia de Luz Próxima ao Infravermelho , Suínos
7.
Neurogastroenterol Motil ; 23(4): 362-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21199176

RESUMO

BACKGROUND: Identification of neuronal progenitor/stem cells in the postnatal gut suggests the development of transplantation approaches to enteric nervous system (ENS) diseases. Many clinical applications would require engrafting large segments of postnatal gut in vivo. We investigated the ability of unselected gut cells vs selected enteric neural crest stem cells (eNCSCs) to engraft and differentiate in the postnatal gut in the Hirschsprung disease (HD, ednrb(sl/sl)) rat. METHODS: Total intestinal cells or eNCSCs (α(4) integrin(+), p75(++)) from embryonic day (E)14.5 rats carrying a marker transgene (human placental alkaline phosphatase, hPAP) were injected intraperitoneally (i.p.) into neonatal HD rats and their healthy littermates. The entire gut was systematically analyzed 3 weeks later for hPAP(+) cells between the serosal surface and the muscularis mucosae. Engrafted cells were examined for HuC/D, S-100B, neuropeptide Y (NPY), neuronal nitric oxide synthase (nNOS), and vasoactive intestinal peptide (VIP) expression. KEY RESULTS: No rats (0/33) injected with unselected cells had hPAP(+) cells in the ENS that expressed neuronal or glial markers. 5/11 healthy and 4/5 HD rats injected with eNCSCs showed widespread but low density engraftment in the ENS with cells expressing neuronal or glial markers. Neurons expressed nNOS and VIP. There was no engraftment in the colon of either HD or wildtype rats. CONCLUSIONS & INFERENCES: Enteric neural crest stem cells will engraft diffusely throughout the postnatal gut of HD rats and differentiate into neurons and glia. Engraftment is not uniform, likely related to age-dependent changes in the gut mesenchyme. Intraperitoneal injection is easily performed in sick neonates and may be developed as a technique to supply exogenous ENS cells to the diseased postnatal gut.


Assuntos
Doença de Hirschsprung/cirurgia , Intestinos/inervação , Crista Neural/transplante , Transplante de Células-Tronco/métodos , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Injeções Intraperitoneais , Neurônios/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Ratos , Ratos Endogâmicos WKY , Peptídeo Intestinal Vasoativo/metabolismo
8.
Meat Sci ; 80(2): 550-4, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22063365

RESUMO

A total of 119 Duroc×(Landrace×Yorkshire) commercial pigs were used to investigate the effect of growth rate (fast vs slow), sex (barrows vs gilts) and slaughter liveweight (107, 115 and 125kg) on the fat characteristics of bellies. Backfat thickness increased with weight (P<0.01). Fat firmness score was only affected by sex (P<0.05), with gilts showing softer bellies than barrows. Fat from gilts and slow growing pigs showed a lower proportion of saturated fatty acids (SFA; P<0.001 and P<0.01, respectively), a higher proportion of linoleic fatty acid (C18:2 n-6; P<0.01), a higher proportion of total polyunsaturated fatty acids (PUFA; P<0.001 and P<0.01, respectively), and an increased iodine value (P<0.001). Consequently, the fat from these bellies had higher PUFA:SFA ratios (P<0.001) and n-6:n-3 ratios (P<0.01 and P<0.001, respectively) than that from the bellies of barrows and fast growing pigs. The belly fat from barrows and fast growing pigs had higher stearic fatty acid (C18:0; P<0.01) and SFA proportions (P<0.001 and P<0.01, respectively) than that from gilts and slow growing pigs. The belly fat from gilts and slow growing pigs would better meet the health requirements of consumers, but it is more prone to rancidity during storage leading to a potentially reduced bacon shelf-life.

9.
Meat Sci ; 76(1): 1-8, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-22064185

RESUMO

Many subjective grading methods with poor repeatability and tedious procedures are still widely used in meat industry. In this study, a hyperspectral-imaging-based technique was investigated to evaluate its potentials for objective determination of pork quality attributes. The system extracted spectral and spatial characteristics simultaneously to determinate the quality attributes, drip loss, pH, and color, of pork meat. Six feature band images were selected for predicting the drip loss (459, 618, 655, 685, 755 and 953nm), pH (494, 571,637, 669, 703 and 978nm) and color (434, 494, 561, 637, 669 and 703nm), respectively. Two intensity indices of the band images were used as inputs to establish neural network models to predict the quality attributes. The results showed that with the hyperspectral-imaging system, the drip loss, pH, and color of pork meat could be predicted with correlation coefficients of 0.77, 0.55 and 0.86, respectively. Pork meat could be classified based on their exudative characteristics and color successfully.

10.
Meat Sci ; 72(1): 91-9, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22061378

RESUMO

Three hundred and forty (340) Duroc×(Landrace×Yorkshire) crossbred piglets were allotted to a 2×2×3 factorial design experiment. The independent variables were the growth rate (fast: around -10 days at 100kg and slow: around +2 days at 100kg), based on two different EBV's (estimated breeding value) of the sire-line for age, the sex (barrows and gilts) and the live weight at slaughter (107, 115 and 125kg). A sub-population of 119 pigs (10 carcasses per treatment) was selected for the carcass and meat quality evaluation trials. As live weight increased there were significant increases in hot carcass weight and dressing percentage (P<0.05). Lean, fat and bone proportions were not affected by weight. Gilts had higher lean proportion (P<0.05) than barrows. Furthermore, carcasses of fast growing pigs were fatter (P<0.05) than those of slower growing ones. Loin muscle pH, drip loss and reflectance values did not vary significantly with any of the treatments. Intramuscular fat was higher in barrows (P<0.05) than in gilts and soluble collagen content decreased with increasing weight (P<0.05). Muscle protein (%) increased (P<0.05) from 107 to 115kg and gilts had a higher (P<0.05) content than castrates. No evidence was found that increasing slaughter weight detracts from carcass characteristics or meat quality.

11.
Meat Sci ; 69(3): 537-43, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22062993

RESUMO

Sixty longissimus (L) muscle chops were selected according to marbling score in order to develop a technique for the quantitative description of marbling fat by means of computer image analysis (CIA) and study its relationship with intramuscular fat content and shear force variation in pork. L muscle samples were taken from gilts belonging to three genetic lines differing in carcass leanness, namely Large White (LW), Meishan-derived dam line (M) and Synthetic Genex 3000 (SG). SG gilts had leaner loins (P<0.001) than LW and M. However, the SG loins were more marbled (P<0.001) and had higher IMF content. In addition, CIA analysis showed that marbling fat was finer and better distributed in the SG line. CIA marbling characteristics were significantly correlated with both IMF content (P<0.001) and shear force values (P<0.05) demonstrating the reliability of this technique to assess the contribution of marbling characteristics to variations in pork eating quality.

12.
Neuroscience ; 124(4): 719-23, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15026112

RESUMO

Homozygous endothelin B receptor deficiency leads to congenital aganglionosis of the gut in rats and mice, equivalent to human Hirschsprung disease. Homozygous endothelin B receptor deficient rats (spotting lethal rats, sl/sl) are characterized not only by this developmental disorder of the enteric nervous system, which limits their life span to 3-4 weeks, but exhibit an increased rate of apoptosis in the dentate gyrus compared to wildtype (+/+) rats. Recently, endothelin B receptor deficient transgenic rescue rats (sl/sl, tg/tg) were created to further investigate the role of the endothelin B receptor in mature animals. Linkage of the human dopamine-beta-hydroxylase promoter to the rat endothelin B receptor gene and expression of this transgenic construct results in normal development of the enteric nervous system. We investigated the expression pattern of this transgenic construct in the brain by using reverse transcriptase polymerase chain reaction. Unexpectedly, transgene mRNA expression was not restricted to the brain stem where adrenergic and noradrenergic nuclei are known to be present but, in addition, was also detectable in hippocampus and cortex. Using in situ tailing technique, cleaved caspase-3 immunohistochemistry and analysis of hematoxylin-eosin-stained serial sections, we found that all studied transgenic animals were rescued from the increased rate of apoptosis in the dentate gyrus characteristic for non-transgenic sl/sl rats. This finding supports our previous observation that the endothelin B receptor might be an important regulatory element supporting cellular survival in the hippocampus during postnatal development. The endothelin B receptor deficient transgenic rescue rats used here are rescued from developmental disorders both in the gut and in the brain.


Assuntos
Encéfalo/metabolismo , Expressão Gênica , Receptor de Endotelina B/deficiência , Receptor de Endotelina B/genética , Terapia de Salvação , Transgenes , Animais , Animais Geneticamente Modificados , Apoptose , Tronco Encefálico/metabolismo , Córtex Cerebral/metabolismo , Giro Denteado/fisiopatologia , Sistema Nervoso Entérico/crescimento & desenvolvimento , Terapia Genética , Doença de Hirschsprung/etiologia , Doença de Hirschsprung/terapia , RNA Mensageiro/metabolismo , Ratos , Ratos Mutantes , Distribuição Tecidual
13.
Occup Environ Med ; 60(9): 693-5, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12937194

RESUMO

Analyses completed on samples collected between 1993 and 1996 showed that about 7% of 475 Inuit newborns from northern Quebec (Canada) had a cord blood lead concentration equal to or greater than 0.48 micromol/l, an intervention level adopted by many governmental agencies. A comparison between the cord blood lead isotope ratios of Inuit and southern Quebec newborns showed that lead sources for these populations were different. Our investigation suggests that lead shots used for game hunting were an important source of lead exposure in the Inuit population. A cohort study conducted in three Inuit communities shows a significant decrease of cord blood lead concentrations after a public health intervention to reduce the use of lead shot. Lead shot ammunition can be a major and preventable source of human exposure to lead.


Assuntos
Dieta/efeitos adversos , Sangue Fetal/química , Inuíte , Chumbo/sangue , Estudos de Coortes , Monitoramento Ambiental/métodos , Feminino , Armas de Fogo , Humanos , Recém-Nascido , Triagem Neonatal , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Quebeque
14.
Poult Sci ; 82(3): 503-9, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12705413

RESUMO

Poultry by-products are not often processed into high-value products. Rather than being transformed into meal for animal feed, a large quantity of chicken skin could be used to produce collagen, which is valued for its unique functional properties. The purpose of this research project was to extract and characterize collagen from chicken skin. Skins were first ground and then were heated to 40 or 60 degrees C to extract the fat. After mechanical separation, the collagen contained in the resulting solid phase was extracted with pepsin or ethylene diamine. Types I and III collagen were then isolated and characterized by SDS PAGE, antigen labeling, determination of tyrosine residues, and transmission electron microscopy. The total collagen content of the skin was recovered from the solid phase following heat treatment at 40 degrees C. Extraction yields varied with the solubilization process: 38.9% of the collagen content in the solid phase was extracted with pepsin and 25.1% with ethylene diamine. Ratios of type I to type III collagen fractionated using NaCl were 74.4:19.8% with pepsin and 62.4:31.7% with ethylene diamine. Characterization tests further revealed the presence of telopeptides solely on ethylene diamine-solubilized collagen. Chicken skin thus appears to be a good alternative source of high-quality collagen.


Assuntos
Galinhas , Colágeno/isolamento & purificação , Pele/química , Animais , Fracionamento Químico , Colágeno/química , Colágeno/ultraestrutura , Colágeno Tipo I/química , Colágeno Tipo I/isolamento & purificação , Colágeno Tipo I/ultraestrutura , Colágeno Tipo III/química , Colágeno Tipo III/isolamento & purificação , Colágeno Tipo III/ultraestrutura , Eletroforese em Gel de Poliacrilamida , Etilenodiaminas , Temperatura Alta , Microscopia Eletrônica , Pepsina A , Cloreto de Sódio , Solubilidade , Tirosina/análise
16.
Am J Physiol Lung Cell Mol Physiol ; 280(5): L1040-8, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11290529

RESUMO

Endothelin (ET)-1 contributes to the regulation of pulmonary vascular tone by stimulation of the ET(A) and ET(B) receptors. Although activation of the ET(A) receptor causes vasoconstriction, stimulation of the ET(B) receptors can elicit either vasodilation or vasoconstriction. To examine the physiological role of the ET(B) receptor in the pulmonary circulation, we studied a genetic rat model of ET(B) receptor deficiency [transgenic(sl/sl)]. We hypothesized that deficiency of the ET(B) receptor would predispose the transgenic(sl/sl) rat lung circulation to enhanced pulmonary vasoconstriction. We found that the lungs of transgenic(sl/sl) rats are ET(B) deficient because they lack ET(B) mRNA in the pulmonary vasculature, have minimal ET(B) receptors as determined with an ET-1 radioligand binding assay, and lack ET-1-mediated pulmonary vasodilation. The transgenic(sl/sl) rats have higher basal pulmonary arterial pressure and vasopressor responses to brief hypoxia or ET-1 infusion. Plasma ET-1 levels are elevated and endothelial nitric oxide synthase protein content and nitric oxide production are diminished in the transgenic(sl/sl) rat lung. These findings suggest that the ET(B) receptor plays a major physiological role in modulating resting pulmonary vascular tone and reactivity to acute hypoxia. We speculate that impaired ET(B) receptor activity can contribute to the pathogenesis of pulmonary hypertension.


Assuntos
Endotelina-1/metabolismo , Hipóxia/metabolismo , Pulmão/metabolismo , Receptores de Endotelina/deficiência , Vasoconstrição/fisiologia , Animais , Animais Geneticamente Modificados , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/genética , Dopamina beta-Hidroxilase/genética , Endotelina-1/farmacologia , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/etiologia , Hibridização In Situ , Técnicas In Vitro , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo III , Regiões Promotoras Genéticas , Artéria Pulmonar/fisiologia , Circulação Pulmonar/efeitos dos fármacos , Circulação Pulmonar/genética , RNA Mensageiro/metabolismo , Ensaio Radioligante , Ratos , Ratos Endogâmicos , Receptor de Endotelina B , Receptores de Endotelina/genética , Receptores de Endotelina/metabolismo , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/genética , Vasoconstrição/efeitos dos fármacos
17.
J Cardiovasc Pharmacol ; 36(5 Suppl 1): S82-5, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11078343

RESUMO

The spotting lethal rat carries a naturally occurring deletion of the endothelin-B- (ET(B)) receptor gene that prevents expression of functional ET(B)-receptors. Gariepy and colleagues used tissue-specific ET(B) transgene expression to support normal enteric nervous system development. To determine functional consequences of ET(B)-receptor deficiency, studies were conducted to characterize the pressor response to endothelin-1 (ET-1) and the ET(B) agonist, sarafotoxin 6c (S6c) in transgenic rats homozygous for the ET(B)-deficiency (sl/sl). Similar transgenic rats heterozygous for the ET(B) deficiency were used as controls (sl/+). All rats were anesthetized with Inactin (100 mg/kg, i.p.) and a tracheostomy performed. The right carotid artery and right jugular veins were catheterized for measuring mean arterial pressure (MAP) and infusion of peptides, respectively. Following baseline measurement of MAP, hexamethonium was infused (10 mg/kg) to block sympathetic reflex responses. After a 10-15 min stabilization period, ET-1 or S6c was infused at 0, 1, 0.3 and 1.0 nmol/kg at 10 min intervals. MAP in the two groups of anesthetized rats was similar during the baseline period. The sl/+ rats showed a classic dose-dependent pressor response to ET-1; a transient vasodilation followed by prolonged vasoconstriction. In contrast, the vasodilation was absent in sl/sl rats. Furthermore, ET-1 was more potent in sl/sl compared to the sl/+ rats. The response to S6c was qualitatively similar to ET-1 in the sl/+ rats. However, the sl/sl rats also had a significant pressor response to the ET(B) agonist, S6c. These studies provide in vivo evidence that the rescued ET(B)-deficient rat lacks functional vasodilatory ET(B) responses in response to ET-1 but retains the vasoconstrictor response to ET(B)-receptor agonists.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Endotelina-1/farmacologia , Receptores de Endotelina/fisiologia , Venenos de Víboras/farmacologia , Animais , Animais Geneticamente Modificados , Relação Dose-Resposta a Droga , Ratos , Receptor de Endotelina B
18.
J Cardiovasc Pharmacol ; 36(5 Suppl 1): S86-9, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11078344

RESUMO

We evaluated the role of endothelin-B- (ET(B)) receptor-mediated action in the development and maintenance of deoxycorticosterone acetate (DOCA)-salt-induced hypertension, cardiovascular hypertrophy and renal damage, using the spotting lethal (sl) rat which carries a naturally occurring deletion in the ET(B)-receptor gene. Homozygous (sl/sl) rats exhibit abnormal development of the neural crest-derived epidermal melanocytes and the enteric nervous system (ENS), and do not live beyond 1 month because of intestinal aganglionosis and resulting intestinal obstruction. Therefore, the dopamine-beta-hydroxylase (D betaH) promoter was used to direct ET(B) transgene expression in sl/sl rats to support normal ENS development. D betaH-ET(B) sl/sl rats live into adulthood and are healthy, expressing ET(B)-receptor in adrenals and other adrenergic neurons. When homozygous (sl/sl) and wild-type (WT) (+/+) rats, all of which were transgenic, were treated with DOCA and salt for 4 weeks, the homozygous rats exhibited significantly earlier and higher increases in systolic blood pressure than WT rats. The daily oral administration of ABT-627, a selective ET(A)-receptor antagonist, almost completely suppressed the DOCA-salt-induced hypertension in both groups. Renal dysfunction and histological damage induced by DOCA-salt treatment were more severe in homozygous than in WT rats. Increased and marked vascular hypertrophy of the aorta was also observed in homozygous rats, compared with WT rats. Renal and vascular injuries induced by DOCA and salt were significantly improved by ABT-627 administration. We propose that ET(B)-receptor-mediated actions are protective factors in the pathogenesis of DOCA-salt-induced hypertension. ET(A)-mediated actions are at least partly responsible for the increased susceptibility to DOCA-salt-induced hypertension and related tissue injuries in ET(B)-receptor-deficient rats.


Assuntos
Desoxicorticosterona/farmacologia , Hipertensão/etiologia , Receptores de Endotelina/fisiologia , Cloreto de Sódio/farmacologia , Animais , Animais Geneticamente Modificados , Pressão Sanguínea/efeitos dos fármacos , Endotelina-1/análise , Endotelina-1/fisiologia , Ratos , Receptor de Endotelina B
19.
Circulation ; 102(22): 2765-73, 2000 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-11094045

RESUMO

BACKGROUND: Endothelin (ET)-1 plays an important role in the pathogenesis of deoxycorticosterone acetate (DOCA)-salt-induced hypertension. We evaluated the pathological role of ET(B) receptors in DOCA-salt-induced hypertension, cardiovascular hypertrophy, and renal damage by using the spotting-lethal (sl) rat, which carries a naturally occurring deletion in the ET(B) receptor gene. METHODS AND RESULTS: Homozygous (sl/sl) rats exhibit abnormal development of neural crest-derived epidermal melanocytes and the enteric nervous system, and they do not live beyond 1 month because of intestinal aganglionosis and intestinal obstruction. The dopamine ss-hydroxylase (DssH) promoter was used to direct ET(B) transgene expression in sl/sl rats to support normal enteric nervous system development. DssH-ET(B) sl/sl rats live into adulthood and are healthy, expressing ET(B) receptors in adrenal glands and other adrenergic neurons. When homozygous (sl/sl) and wild-type (+/+) rats, all of which were transgenic, were treated with DOCA-salt, homozygous rats exhibited earlier and higher increases in systolic blood pressure than did wild-type rats. Chronic treatment with ABT-627, an ET(A) receptor antagonist, completely suppressed DOCA-salt-induced hypertension in both groups. Renal dysfunction and histological damage were more severe in homozygous than in wild-type rats. Marked vascular hypertrophy was observed in homozygous rats than in wild-type rats. Renal and vascular injuries were significantly improved by ABT-627. In DOCA-salt-treated homozygous rats, there were notable increases in renal, urinary, and aortic ET-1, all of which were normalized by ABT-627. CONCLUSIONS: ET(B)-mediated actions are protective in the pathogenesis of DOCA-salt-induced hypertension. Enhanced ET-1 production and ET(A)-mediated actions are responsible for the increased susceptibility to DOCA-salt hypertension and tissue injuries in ET(B) receptor-deficient rats.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Desoxicorticosterona/farmacologia , Hipertensão/fisiopatologia , Rim/efeitos dos fármacos , Receptores de Endotelina/deficiência , Acetilglucosaminidase/urina , Animais , Animais Geneticamente Modificados , Aorta/efeitos dos fármacos , Aorta/patologia , Nitrogênio da Ureia Sanguínea , Peso Corporal/efeitos dos fármacos , Endotelina-1/sangue , Endotelina-1/efeitos dos fármacos , Endotelina-1/urina , Coração/efeitos dos fármacos , Coração/fisiopatologia , Hipertensão/induzido quimicamente , Hipertensão/patologia , Rim/patologia , Rim/fisiopatologia , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Mutantes , Receptor de Endotelina B , Receptores de Endotelina/genética , Sístole , Fatores de Tempo
20.
Curr Opin Nephrol Hypertens ; 9(4): 435-9, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10926181

RESUMO

The role of the endothelin-B receptor in vascular homeostasis is controversial because the receptor has both pressor and depressor effects in vivo. One potential depressor mechanism of endothelin-B activation is through the promotion of natriuresis and diuresis in the renal tubule. Recent studies demonstrate that rodents genetically deficient for the endothelin-B exhibit sodium-dependent hypertension due to an absence of tonic inhibition of the epithelial sodium channel in the distal nephron. These studies suggest that the predominant role of endothelin-B receptors in the basal physiologic state may be to regulate renal sodium excretion relative to the level of oral salt intake.


Assuntos
Fenômenos Fisiológicos Cardiovasculares , Hipertensão/fisiopatologia , Túbulos Renais/fisiologia , Rim/fisiologia , Receptores de Endotelina/fisiologia , Animais , Espaço Extracelular/fisiologia , Homeostase , Humanos , Túbulos Renais/fisiopatologia , Modelos Biológicos , Receptor de Endotelina B , Transdução de Sinais , Equilíbrio Hidroeletrolítico
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