RESUMEN
Sedimentary basins increase the damaging effects of earthquakes by trapping and amplifying seismic waves. Simulations of seismic wave propagation in sedimentary basins capture this effect; however, there exists no method to validate these results for earthquakes that have not yet occurred. We present a new approach for ground motion prediction that uses the ambient seismic field. We apply our method to a suite of magnitude 7 scenario earthquakes on the southern San Andreas fault and compare our ground motion predictions with simulations. Both methods find strong amplification and coupling of source and structure effects, but they predict substantially different shaking patterns across the Los Angeles Basin. The virtual earthquake approach provides a new approach for predicting long-period strong ground motion.
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Simulación por Computador , Planificación en Desastres/métodos , Terremotos , Modelos Teóricos , Predicción , Sedimentos Geológicos , Movimiento (Física)RESUMEN
The Kuiper belt is a collection of small bodies (Kuiper belt objects, KBOs) that lie beyond the orbit of Neptune and which are believed to have formed contemporaneously with the planets. Their small size and great distance make them difficult to study. KBO 55636 (2002 TX(300)) is a member of the water-ice-rich Haumea KBO collisional family. The Haumea family are among the most highly reflective objects in the Solar System. Dynamical calculations indicate that the collision that created KBO 55636 occurred at least 1 Gyr ago. Here we report observations of a multi-chord stellar occultation by KBO 55636, which occurred on 9 October 2009 ut. We find that it has a mean radius of 143 +/- 5 km (assuming a circular solution). Allowing for possible elliptical shapes, we find a geometric albedo of in the V photometric band, which establishes that KBO 55636 is smaller than previously thought and that, like its parent body, it is highly reflective. The dynamical age implies either that KBO 55636 has an active resurfacing mechanism, or that fresh water-ice in the outer Solar System can persist for gigayear timescales.
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Ten days of photometric data were obtained during the commissioning phase of the Kepler mission, including data for the previously known giant transiting exoplanet HAT-P-7b. The data for HAT-P-7b show a smooth rise and fall of light from the planet as it orbits its star, punctuated by a drop of 130 +/- 11 parts per million in flux when the planet passes behind its star. We interpret this as the phase variation of the dayside thermal emission plus reflected light from the planet as it orbits its star and is occulted. The depth of the occultation is similar in photometric precision to the detection of a transiting Earth-size planet for which the mission was designed.
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Of the 18 trematode species that use the horn snail, Cerithidea californica, as a first intermediate host, 6 have the potential to use raccoons as a final host. The presence of raccoon latrines in Carpinteria Salt Marsh, California, allowed us to investigate associations between raccoons and trematodes in snails. Two trematode species, Probolocoryphe uca and Stictodora hancocki, occurred at higher prevalences in snails near raccoon latrines than in snails away from latrines, suggesting that raccoons may serve as final hosts for these species. Fecal remains indicated that raccoons fed on shore crabs, the second intermediate host for P. uca, and fish, the second intermediate host for S. hancocki. The increase in raccoon populations in the suburban areas surrounding west coast salt marshes could increase their importance as final hosts for trematodes in this system.
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Heterophyidae/aislamiento & purificación , Mapaches/parasitología , Caracoles/parasitología , Trematodos/aislamiento & purificación , Infecciones por Trematodos/veterinaria , Animales , Aves , Braquiuros/parasitología , California/epidemiología , Heces/parasitología , Peces/parasitología , Heterophyidae/fisiología , Prevalencia , Trematodos/fisiología , Infecciones por Trematodos/epidemiología , Infecciones por Trematodos/transmisiónRESUMEN
Stellar occultations--the passing of a relatively nearby body in front of a background star--can be used to probe the atmosphere of the closer body with a spatial resolution of a few kilometres (ref. 1). Such observations can yield the scale height, temperature profile, and other information about the structure of the occulting atmosphere. Occultation data acquired for Pluto's atmosphere in 1988 revealed a nearly isothermal atmosphere above a radius of approximately 1,215 km. Below this level, the data could be interpreted as indicating either an extinction layer or the onset of a large thermal gradient, calling into question the fundamental structure of this atmosphere. Another question is to what extent Pluto's atmosphere might be collapsing as it recedes from the Sun (passing perihelion in 1989 in its 248-year orbital period), owing to the extreme sensitivity of the equilibrium surface pressure to the surface temperature. Here we report observations at a variety of visible and infrared wavelengths of an occultation of a star by Pluto in August 2002. These data reveal evidence for extinction in Pluto's atmosphere and show that it has indeed changed, having expanded rather than collapsed, since 1988.
RESUMEN
Nitrogen dioxide (NO2) is a free radical-producing oxidant gas. Inhalation of NO2 could cause airway inflammation, and decrease immune function. This experiment tested the hypothesis that exposure to NO2 would: 1) increase leukocytes in bronchoalveolar lavage (BAL); and 2) change the distribution of lymphocyte subsets and activation in BAL and peripheral blood (PB). Using a counter-balanced, repeated-measures design, 15 healthy volunteers were exposed to filtered air (FA) or 2.0 parts per million NO2 for 4 h x day(-1) (4 x 30 min of exercise), for three consecutive days. Bronchoscopy was performed 18 h following each exposure set, and PB was drawn pre-exposure and pre-bronchoscopy. Flow cytometry was used to enumerate lymphocyte subsets and activation makers in BAL and PB. In the bronchial fraction, there was an increase in the percentage of neutrophils following NO2 exposure compared to FA (median (interquartile range): 10.6 (4.8-17.2)% versus 5.3 (2.5-8.3)%; p=0.005). In the BAL, there was a decrease in the percentage of T-helper cells following NO2 exposure compared to FA (55.9 (40.8-62.7)% versus 61.6 (52.6-65.2)%; p=0.022). For PB, there were no between-condition differences in any leukocyte or lymphocyte subsets, or activation. In conclusion exposure to nitrogen dioxide results in bronchial inflammation and a minimal change in bronchoalveolar lavage T-helper cells, and no changes in peripheral blood cells.
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Líquido del Lavado Bronquioalveolar/citología , Leucocitos/efectos de los fármacos , Subgrupos Linfocitarios/efectos de los fármacos , Dióxido de Nitrógeno/farmacología , Adulto , Sangre , Femenino , Humanos , MasculinoRESUMEN
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the effects of agonists like 2,3, 7,8-tetrachlorodibenzo-p-dioxin. In the current model for AHR signaling, the unliganded receptor is found in the cytosol as part of a complex with a dimer of the 90-kDa heat shock protein and an immunophilin-like molecule, ARA9. In yeast, expression of ARA9 results in an increase in the maximal agonist response and a leftward shift in the AHR dose-response curve. To better understand the mechanism by which ARA9 modifies AHR signal transduction, we performed a series of coexpression experiments in yeast and mammalian cells. Our results demonstrate that ARA9's influence on AHR signaling is not due to inhibition of a membrane pump or modification of the receptor's transactivation properties. Using receptor photoaffinity labeling experiments, we were able to show that ARA9 enhances AHR signal transduction by increasing the available AHR binding sites within the cytosolic compartment of the cell. Our evidence suggests that ARA9's effects are related to its role as a cellular chaperone; i.e. we observed that expression of ARA9 increases the fraction of AHR in the cytosol and also stabilized the receptor under heat stress.
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Proteínas Portadoras/metabolismo , Proteínas , Receptores de Hidrocarburo de Aril/genética , Transducción de Señal , Animales , Sitios de Unión , Células COS , Línea Celular , Citosol/metabolismo , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intracelular , Chaperonas Moleculares/metabolismo , Etiquetas de Fotoafinidad , Desnaturalización Proteica , Receptores de Hidrocarburo de Aril/agonistas , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Saccharomyces cerevisiae , Transducción de Señal/efectos de los fármacos , Tacrolimus/farmacología , Activación Transcripcional , TransfecciónRESUMEN
The unliganded aryl hydrocarbon receptor (AHR) is found in a complex with other proteins including the 90-kDa heat shock protein (Hsp90) and a 37-kDa protein we refer to as ARA9. We found that the three tetratricopeptide repeats found in the COOH terminus of ARA9 are necessary and sufficient for interaction with the AHR complex. Conversely, the AHR's "repressor"/Hsp90 binding domain is required for interaction with ARA9. Because ARA9 closely resembles the 52-kDa FK506-binding protein (FKBP52), found in the unliganded glucocorticoid receptor (GR) complex, we compared the binding specificities of ARA9 and FKBP52 for AHR and GR. In co-immunoprecipitation experiments, ARA9 specifically associated with AHR-Hsp90 complex but not with GR-Hsp90 complexes. In addition, ARA9 showed a greater capacity than FKBP52 to associate with AHR-Hsp90 complexes. The biological importance of this interaction was suggested by the observation that in a yeast expression system ARA9 expression enhanced the response of AHR to the agonist beta-napthoflavone, decreasing the EC50 by greater than 5-fold and increasing the maximal response 2.5-fold. In contrast, co-expression of FKBP52 had no effect on AHR signaling. In addition, although ARA9 contains a domain similar to that found in other FK506-binding proteins, ARA9 binding to 3H-FK506 could not be detected. Finally, we have characterized the developmental and expression pattern of ARA9 in the developing mouse embryo and mapped the ARA9 locus to human chromosome 11q13.3.
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Proteínas Portadoras/metabolismo , Proteínas , Animales , Secuencia de Bases , Proteínas Portadoras/genética , Mapeo Cromosómico , Cartilla de ADN , Regulación del Desarrollo de la Expresión Génica , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular , Ratones , Unión Proteica , Receptores de Hidrocarburo de Aril/metabolismo , Saccharomyces cerevisiae/genética , Tacrolimus/metabolismoRESUMEN
Beta 7 integrins serve special roles in mucosal immunity. Alpha 4 beta 7-mediated adhesion to mucosal addressin cell adhesion molecule-1 (MAdCAM-1) directs lymphocyte homing to the gut, and alpha E beta 7 mediates binding of lymphocytes to E-cadherin on epithelial cells. Since alpha 4 beta 7 mediates adhesion to MAdCAM-1 but alpha 4 beta 1 does not, we used beta 7/beta 1 chimeras to directly assess the importance of specific regions of beta 7 in MAdCAM-1 binding. We found a region of beta 7 (residues 46-386) that accounts for specificity of alpha 4 beta 7 binding to MAdCAM-1. We also used human/mouse and human/rat chimeric beta 7 subunits to map epitopes recognized by fifteen anti-beta 7 mAbs. Six of seven Abs that block adhesion to MAdCAM-1 and E-cadherin (Fib 21, 22, 27, 30, 504; Act-1) mapped to amino acid residues 176-250. Residues 176-250 lie within the region of beta 7 that specifies MAdCAM-1 binding and also within a region that has a predicted structure homologous to the metal ion-dependent adhesion site (MIDAS) domains of the integrin subunits alpha L and alpha M. Three new Abs that recognize beta 7 in the presence of Mn2+, but not Ca2+, and promote adhesion to MAdCAM-1, mapped to amino acids 46-149. One blocking and five other Abs mapped to other regions (amino acids 387-725). We conclude that a MIDAS-like domain serves a critical role in beta 7 integrin-mediated adhesion.
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Inmunoglobulinas/metabolismo , Cadenas beta de Integrinas , Integrinas/química , Integrinas/fisiología , Mucoproteínas/metabolismo , Estructura Terciaria de Proteína , Receptores Mensajeros de Linfocitos/metabolismo , Animales , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/fisiología , Cationes , Moléculas de Adhesión Celular , Mapeo Epitopo , Humanos , Inmunoglobulinas/inmunología , Integrinas/genética , Integrinas/inmunología , Leucemia Eritroblástica Aguda/metabolismo , Ligandos , Ratones , Datos de Secuencia Molecular , Mucoproteínas/inmunología , Unión Proteica/inmunología , Ratas , Proteínas Recombinantes de Fusión/química , Serina/inmunología , Serina/fisiología , Relación Estructura-Actividad , Transfección/inmunología , Células Tumorales CultivadasRESUMEN
In this review, we present background material that provides partial support for a tissue renin-angiotensin system (RAS). Evidence for the existence of this system relied in part on the use of drugs, which has entailed using low doses or concentrations of angiotensin-converting enzyme inhibitors, renin inhibitors, and angiotensin antagonists to block the RAS in vascular beds and in isolated arteries or organs. Other evidence for a tissue RAS has depended upon measurements of the components of the system, i.e. enzymes, substrates, and mRNAs for these proteins. All of these components were first believed to be present in the heart and blood vessels; however, it is now known that renin in the circulating blood derived from the kidney is used for the local synthesis of angiotensins. The main emphasis of the review is on the renal RAS because it is believed that the local RAS is most prominent in this organ. The renal RAS is probably involved in the long-rather than short-term regulation of renal vascular resistance and maintenance of normal blood pressure through the regulation of sodium reabsorption.
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Sistema Renina-Angiotensina/efectos de los fármacos , Angiotensina II/biosíntesis , Angiotensina II/sangre , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/fisiología , Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/fisiología , Renina/sangre , Sistema Renina-Angiotensina/fisiologíaRESUMEN
The detection of terrestrial-sized extrasolar planets from the ground has been thought to be virtually impossible due to atmospheric scintillation limits. However, we show that this is not the case especially selected (but nevertheless main sequence) stars, namely small eclipsing binaries. For the smallest of these systems, CM Draconis, several months to a few years of photometric observations with 1-m-class telescopes will be sufficient to detect the transits of any short-period planets of sizes > or = 1.5 Earth radii (RE), using cross-correlation analysis with moderately good photometry. Somewhat larger telescopes will be needed to extend this detectability to terrestrial planets in larger eclipsing binary systems. (We arbitrarily define "terrestrial planets" herein as those whose disc areas are closer to that of Earth's than Neptune's i.e., less than about 2.78 RE.) As a "spin-off" of such observations, we will also be able to detect the presence of Jovian-mass planets without transits using the timing of the eclipse minima. Eclipse minima will drift in time as the binary system is offset by a sufficiently massive planet (i.e., one Jupiter mass) about the binary/giant-planet barycenter, causing a periodic variation in the light travel time to the observer. We present here an outline of present observations taking place at the University of California Lick Observatory using the Crossley 0.9-m telescope in collaboration with other observatories (in South Korea, Crete, France, Canary Islands, and New York) to detect or constrain the existence of terrestrial planets around main sequence eclipsing binary star systems, starting with CM Draconis. We demonstrate the applicability of photometric data to the general detection of gas giant planets via eclipse minima timings in many other small-mass eclipsing binary systems as well.
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Astronomía/métodos , Planetas , Astronomía/instrumentación , Medio Ambiente Extraterrestre , FotometríaRESUMEN
On the basis of evidence suggesting the activation of the kallikrein-kinin system in steroid-induced hypertension, we considered the possibility that the angiotensin-converting enzyme inhibitor captopril would lower the arterial blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats through kininase II inhibition. In conscious DOCA-salt hypertensive rats with intact kidneys (n = 6) or uninephrectomized rats (n = 5), the short-term administration of captopril (8 mg/kg IV) decreased mean blood pressure from 141 +/- 3 to 118 +/- 3 mm Hg (P < .05) and from 176 +/- 12 to 158 +/- 15 mm Hg (P < .05), respectively. The maximal effect of captopril was manifested between 40 and 50 minutes after its administration, and blood pressure remained depressed for at least 2 hours. The bradykinin B2 receptor antagonist Hoe 140 (500 micrograms/kg IV) abolished the antihypertensive effect of captopril in the DOCA-salt hypertensive rats, indicating kinin involvement. Losartan, an angiotensin type 1 receptor antagonist, had no effect on blood pressure in another group of DOCA-salt hypertensive rats (n = 9) and did not significantly change the response to captopril. No effect of the angiotensin-converting enzyme inhibitor was seen in normotensive control rats (n = 5), indicating the absence of a nonspecific hypotensive action of the drug. Plasma renin activity was lower in the DOCA-salt hypertensive rats (0.7 +/- 0.2 ng angiotensin I/mL per hour, n = 4) than in normotensive control rats (8.8 +/- 1.7, n = 4). The involvement of kinins in the antihypertensive effect of captopril in DOCA-salt hypertension supports the contention that the kallikrein-kinin system contributes to blood pressure regulation in this hypertension model.
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Captopril/farmacología , Desoxicorticosterona , Hipertensión/inducido químicamente , Hipertensión/fisiopatología , Cininas/fisiología , Cloruro de Sodio , Angiotensina II/antagonistas & inhibidores , Animales , Antiinflamatorios no Esteroideos/farmacología , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Bradiquinina/análogos & derivados , Bradiquinina/farmacología , Cininas/antagonistas & inhibidores , Masculino , Nefrectomía , Ratas , Ratas Wistar , Valores de Referencia , Circulación Renal/efectos de los fármacos , Factores de TiempoRESUMEN
OBJECTIVE: To probe the potential influence of a high renal tubular level of angiotensin II on sodium reabsorption using angiotensin converting enzyme inhibitors and a non-peptide angiotensin antagonist. METHODS: Systemic arterial blood pressure, renal blood flow (RBF) and electrolyte and urinary excretion were measured in anesthetized uninephrectomized Wistar rats. Captopril (n = 12), ramiprilat (n = 10) or EXP 3174 (n = 9) was infused into the renal artery in graded doses to examine whether the threshold dose that increased RBF was lower than that which increased sodium excretion rate (Na+ excretion rate). RESULTS: Whereas ramiprilat (0.5-4 micrograms/kg/min intra-arterially) and EXP 3174 (0.5-4 micrograms/kg/min intra-arterially) decreased blood pressure in all but the lowest dose of 0.5 micrograms/kg/min, captopril (1-8 micrograms/kg/min intra-arterially) did not change blood pressure except for a slight effect with the two higher doses. These three agents increased RBF to about the same degree, between 6% and 18%, which was relatively large compared with the maximal vasodilator response achievable in the kidney with acetylcholine (30-37%). Captopril given intra-arterially had a more consistent effect on Na+ excretion rate than either ramiprilat or EXP 3174. An increase in Na+ excretion rate occurred with captopril ranging from 44% to 78%, whereas no significant change was obtained with the other drugs. The dose of captopril that increased RBF was the same as that which increased Na+ excretion rate. In those experiments in which ramiprilat resulted in an increase in Na+ excretion rate (five of 10 experiments), the effective dose was the same as that which increased RBF. CONCLUSION: When administered by the intra-arterial route, captopril was more effective in increasing Na+ excretion rate than either ramiprilat or EXP 3174. Although the threshold dose of captopril and ramiprilat required to increase Na+ excretion rate and RBF was similar, suggesting blockade of a common angiotensin II pool, there was not a good correlation between these two effects.
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Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Natriuresis/efectos de los fármacos , Circulación Renal/efectos de los fármacos , Angiotensina II/antagonistas & inhibidores , Animales , Captopril/farmacología , Umbral Diferencial/efectos de los fármacos , Diuresis/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Imidazoles/farmacología , Losartán , Nefrectomía , Potasio/orina , Ramipril/análogos & derivados , Ramipril/farmacología , Ratas , Ratas Wistar , Tetrazoles/farmacología , Vasodilatación/efectos de los fármacosRESUMEN
We tested the hypothesis that early alterations in calcium influx induced by an imposed 60 Hz magnetic field are propagated down the signal transduction (ST) cascade to alter c-MYC mRNa induction. To test this we measured both ST parameters in the same cells following 60 Hz magnetic field exposures in a specialized annular ring device (220 G (22 mT), 1.7 mV/cm maximal E(induced), 37 degrees C, 60 min). Ca2+ influx is a very early ST marker that precedes the specific induction of mRNA transcripts for the proto-oncogene c-MYC, an immediate early response gene. In three experiments influx of 45Ca2+ in the absence of mitogen was similar to that in cells treated with suboptimal levels of Con-A (1 micrograms/ml). However, calcium influx was elevated 1.5-fold when lymphocytes were exposed to Con-A plus magnetic fields; this co-stimulatory effect is consistent with previous reports from our laboratory [FEBS Lett. 301 (1992) 53-59; FEBS Lett. 271 (1990) 157-160; Ann. N.Y. Acad. Sci. 649 (1992) 74-95]. The level of c-MYC mRNA transcript copies in non-activated cells and in suboptimally-activated cells was also similar, which is consistent with the above calcium influx findings. Significantly, lymphocytes exposed to the combination of magnetic fields plus suboptimal Con-A responded with an approximate 3.0-fold increase in band intensity of c-MYC mRNA transcripts. Importantly, transcripts for the housekeeping gene GAPDH were not influenced by mitogen or magnetic fields. We also observed that lymphocytes that failed to exhibit increased calcium influx in response to magnetic fields plus Con-A, also failed to exhibit an increase in total copies of c-MYC mRNA. Thus, calcium influx and c-MYC mRNA expression, which are sequentially linked via the signal transduction cascade in contrast to GAPDH, were both increased by magnetic fields. These findings support the above ST hypothesis and provide experimental evidence for a general biological framework for understanding magnetic field interactions with the cell through signal transduction. In addition, these findings indicate that magnetic fields can act as a co-stimulus at suboptimal levels of mitogen; pronounced physiological changes in lymphocytes such as calcium influx and c-MYC mRNA induction were not triggered by a weak mitogenic signal unless accompanied by a magnetic field. Magnetic fields, thus, have the ability to potentiate or amplify cell signaling.
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Calcio/metabolismo , Magnetismo , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Transducción de Señal , Animales , Northern Blotting , Inducción Enzimática , Gliceraldehído-3-Fosfato Deshidrogenasas/genética , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Timo/metabolismoRESUMEN
Platelet activating factor (PAF) is produced by the rat renal papilla from a neutral lipid, alkylacetylglycerol. Renal release of another neutral lipid, antihypertensive neutral renomedullary lipid, and PAF might account for normalization of blood pressure after unclipping in Goldblatt hypertensive rats. We studied the potential storage and release of hypotensive substances by the rat renal papilla in vitro. Rat kidneys were snap-frozen in liquid N2-cooled freon immediately after removal and the total lipids were extracted from pooled dissected papillae and partially separated by thin layer chromatography on silica gel with a hexane: ether: acetic acid (40:60:1) solvent system. Lipids eluted from four, contiguous silica gel zones were assayed in anesthetized spontaneously hypertensive rats. No hypotensive activity was found in the thin layer chromatography lipid fraction co-migrating with palmitylacetylglycerol or in any other neutral lipid fraction. In contrast, the Krebs medium obtained after 30-min incubation of freshly minced papillary tissue induced dose-related hypotension and bradycardia. The hypotensive activity was equivalent to 48 +/- 9 ng prostaglandin E2 (PGE2)/mg wet papilla. Bradycardia induced by the incubation medium was correlated with decrements in blood pressure. In the same assays, nitroprusside caused tachycardia which was correlated with hypotension, and the bradycardia associated with PGE2-induced hypotension was significantly less than that induced by the incubation medium. The dose-related effects of the incubation medium were dramatically attenuated by indomethacin treatment of the papilla, suggesting that the hypotensive activity is dependent upon papillary cyclooxygenase activity. However, PGI2 elicited hypotension concomitant with tachycardia rather than bradycardia and PGE2 did not mimic the incubation medium-induced bradycardia. Therefore, the effects of the papillary incubation medium may be mediated by other cyclooxygenase metabolites. Production/release of hypotensive material by indomethacin-treated papillary tissue was potentiated by co-incubation with non-hypotensive quantities of PGE2, suggesting a potential role for PGE2 in the renal antihypertensive function. Increasing pressure on the papilla from 6 to 20 mmHg during incubation did not increase release of non-prostanoid hypotensive substance(s). These results suggest that the formation and release of cyclooxygenase metabolites accounts primarily for the hypotensive activity released from rat renal papillae in vitro, and that prostaglandins might play a permissive role in the release of other renomedullary hypotensive substances.
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Presión Sanguínea/fisiología , Médula Renal/metabolismo , Metabolismo de los Lípidos , Animales , Cromatografía en Capa Delgada , Dinoprostona/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Técnicas In Vitro , Indometacina/farmacología , Médula Renal/química , Médula Renal/efectos de los fármacos , Lípidos/aislamiento & purificación , Masculino , Nitroprusiato/farmacología , Ratas , Ratas Endogámicas SHR , Ratas EndogámicasRESUMEN
Removal of the arterial clip (unclipping) in one-kidney, one-clip (1K, 1C) Goldblatt hypertensive rats causes rapid return of mean arterial pressure (MAP) to normotensive levels. An extracorporeal circulation was established between the renal and jugular veins to evaluate the influence of unclipping on renal blood flow (RBF) in Inactin-anesthetized 1K, 1C rats. MAP in rats with the extracorporeal circulation was 182 +/- 5 mmHg before unclipping or sham operation. MAP decreased to 113 +/- 4 mmHg within 2 h after unclipping compared with 169 +/- 13 mmHg in sham-unclipped rats. RBF increased by 2.8 ml.min-1.g-1 from a basal level of 3.8 +/- 0.3 after unclipping and was maintained approximately 40% above the basal level for 2 h, although renal vascular resistance was 94% greater than in uninephrectomized control rats. Heart rate did not change in either unclipped or sham-operated rats. Indomethacin (7 mg/kg) did not affect unclipping-induced changes in MAP, RBF, or urine output; however heart rate decreased immediately after unclipping and remained approximately 25-35 beats/min below control levels for the 2-h observation period. In rats lacking the extracorporeal circuit, MAP decreased (P less than 0.005) and heart rate increased (P less than 0.05) in response to unclipping. Nevertheless, unclipping-induced tachycardia was significantly less than that caused by nitroprusside infusions causing similar decrements in MAP. The results suggest that the sustained increment in RBF after unclipping in chronic, established 1K, 1C hypertension may be associated with postunclipping hypotension and diuresis, that blockade of prostaglandin synthesis may unmask unclipping-induced bradycardia, and that prostaglandins are not essential for postunclipping changes in renal hemodynamics.
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Hipertensión Renovascular/fisiopatología , Circulación Renal , Reperfusión , Animales , Presión Sanguínea/efectos de los fármacos , Constricción , Circulación Extracorporea , Hemodinámica , Indometacina/farmacología , Masculino , Ratas , Circulación Renal/efectos de los fármacosRESUMEN
The hemodynamic effects of platelet activating factor (PAF), PAF antagonists and a precursor of PAF, 1-palmityl-2-acetyl-glycerol (PAG), were examined in pentobarbital-anesthetized spontaneously hypertensive rats to determine whether functionally significant amounts of PAF are produced via the cholinephosphotransferase pathway of PAF synthesis in vivo. Intravenous bolus doses of PAF, PAG and nitroprusside elicited hypotension and active mesenteric vasodilatation. Responses to PAG were slower in onset and longer in duration than those of PAF and nitroprusside. The specific PAF antagonists, CV-3988 and SRI 63-675, attenuated PAG- and PAF-, but not nitroprusside-induced changes in blood pressure and mesenteric flow/resistance. In contrast, captopril, which blocked the effects of angiotensin I, did not influence the hypotension caused by PAG, PAF and nitroprusside. The results suggest that the vasodilator effects of PAG are attributable to PAF produced from this alkylacetylglycerol, and the renin-angiotensin system does not appear to influence the biotransformation of PAG to PAF or the hypotensive action of PAF.
Asunto(s)
Éteres de Glicerilo/farmacología , Hemodinámica/efectos de los fármacos , Factor de Activación Plaquetaria/biosíntesis , Vasodilatadores/farmacología , Animales , Captopril/farmacología , Diacilglicerol Colinafosfotransferasa/fisiología , Masculino , Nitroprusiato/farmacología , Éteres Fosfolípidos/farmacología , Factor de Activación Plaquetaria/fisiología , Quinolinas/farmacología , Ratas , Ratas Endogámicas SHRRESUMEN
Studies were conducted to determine whether reduced renal blood flow (RBF) exhibited by rats with uncontrolled streptozotocin (STZ)-induced diabetes is attributable to diabetes-induced structural changes in the renal vasculature. Vehicle-treated control rats (CR) and rats that were injected with STZ (STZR) after pretreatment with 3-O-methylglucose (3-OMG), an agent that prevents STZ-induced hyperglycemia, were also studied. Basal values of total RBF (ml.min-1.g kidney wt-1, electromagnetic flow probe), systemic arterial pressure (BP, mmHg), and renal vascular resistance (RVR, BP/RBF) in pentobarbital-anesthetized rats during a control period were 5.4 +/- 0.3 (P less than 0.01 vs. CR), 116 +/- 3, and 21.9 +/- 1.0 (P less than 0.01 vs. CR) in STZR (n = 12) and 8.2 +/- 0.4, 121 +/- 2, and 15.3 +/- 1.0 in CR (n = 11), respectively. Basal values of RBF, BP, and RVR in 3-OMG-pretreated STZR were identical to CR. The relative capacity of STZR and CR kidneys for vasodilatation in situ in response to intrarenal arterial infusions of acetylcholine (ACh) and bradykinin (BK) and systemically administered sodium nitroprusside (NP) was evaluated. The capacity of STZR to exhibit active renal vasodilatation in response to intrarenal arterial ACh and BK was significantly less than that of CR (P less than 0.01). The minimum level to which RVR was suppressed after 50 micrograms NP/kg iv was higher in STZR than in either CR or 3-OMG-pretreated STZR (14.8 +/- 1.5 vs. 9.0 +/- 0.7 and 9.3 +/- 1.5 mmHg.ml-1.min.g kidney wt, respectively; P less than 0.05). This dose of NP exerted effective functional antagonism of renal vasoconstriction induced by exogenous norepinephrine and angiotensin II. These in vivo studies suggest that the elevated RVR in STZR might be attributable in part to structural changes in the renal vasculature that are associated with the diabetic state and limit the capacity for renal vasodilatation. However, there was no difference in pressure-flow relationships between the two groups in maximally dilated isolated kidneys perfused with Krebs buffer containing 5% albumin, and the RBF deficit in STZR kidneys was corrected by perfusion with blood from CR. Thus the decreased RBF exhibited by STRZ in vivo cannot be attributed solely to renal vascular structural changes associated with diabetes. These findings suggest that undefined humoral factors or abnormal interaction of formed blood elements with vessel walls may account for elevated RVR in STZR.
Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Riñón/irrigación sanguínea , Vasodilatación , 3-O-Metilglucosa , Acetilcolina/farmacología , Angiotensina II/farmacología , Animales , Bradiquinina/farmacología , Desnervación , Circulación Extracorporea , Hemodinámica , Riñón/inervación , Masculino , Metilglucósidos/farmacología , Nitroprusiato/farmacología , Norepinefrina/farmacología , Ratas , Ratas Endogámicas , Flujo Sanguíneo RegionalRESUMEN
Systemic arterial pressure and renal blood flow were measured in pentobarbital-anesthetized spontaneously hypertensive rats to assess the influence and mechanism of action of metabolically stable adenosine analogs on renal hemodynamics. (-)-Aristeromycin (carbocyclic adenosine; CA), a model carbocyclic nucleoside, was characterized with respect to adenosine receptor pharmacology by comparison to the effects elicited by the prototypic adenosine analogs 5'-N-ethylcarboxamide adenosine (NECA; an adenosine A1 and A2 receptor agonist) and N6-cyclohexyl adenosine (an adenosine A1 agonist). Intravenous bolus injections of CA and NECA caused dose-dependent hypotension and renal vasodilatation. Although CA and NECA were equally efficacious hypotensive agents, NECA was approximately 100-fold more potent than CA. CA was a more efficacious renal vasodilator than NECA. In contrast, at doses which had minimal effects on systemic arterial pressure, N6-cyclohexyl adenosine decreased renal blood flow. The hypotensive and renovascular effects of the adenosine analogs but not those of a control vasodilator, methacholine, were attenuated by i.v. administration of the xanthines aminophylline and 8-phenyltheophylline; thus, the effects of the nucleosides on renal blood flow in vivo appear to be attributable in part to activation of adenosine receptors. The profile of cardiovascular effects caused by CA suggests that this agent acts primarily as an adenosine A2 receptor agonist.