RESUMEN

Blarinomys breviceps possesses cryptic and burrowing habits with poorly documented genetics and life history traits. Due to its rarity, only a few specimens and DNA sequences have been deposited in collections worldwide. Here, we present the most comprehensive cytogenetic and molecular characterization of this rare genus. Phylogenetic analyses based on partial cytochrome b sequences were performed, attempting to establish the relationships among individuals with distinct karyotypes along the geographic distribution of the genus in the Atlantic Forest. Classical and molecular cytogenetics, using banding patterns and FISH of telomeric and whole chromosome X-specific painting probes (obtained from the Akodontini Akodon cursor) were used to characterize and compare the chromosomal complements. Molecular phylogenetic analyses recovered 2 main geographically structured clades, northeastern and southeastern with pairwise sequence divergences among specimens varying between 4.9 and 8.4%. Eight distinct karyomorphs are described: (A) 2n = 52 (50A, XX), (B) 2n = 52 (48A, XY+2Bs), (C) 2n = 45 (42A, XY+1B), (D) 2n = 43 (37A, XX+4Bs), (E) 2n = 37 (34A, XY+1B), (F) 2n = 34 (32A, XX), (G) 2n = 31 (27A, XX+2Bs), (H) 2n = 28 (26A, XY), all with the same number of autosomal arms (FN(A) = 50). Variation of 0-4 supernumerary chromosomes (Bs) presenting heterogeneity in morphology and distribution of interstitial telomeric sequences (ITSs) is reported. ITSs are also found in some metacentric autosomes. The phylogeographic separation between 2 major lineages with high levels of genetic divergence, and the wide karyotypic diversity indicate that B. breviceps is a diverse group that warrants taxonomic re-evaluation.

Asunto(s)

Filogenia , Sigmodontinae/genética , Animales , Brasil , Cariotipificación , Filogeografía

RESUMEN

Deltamys Thomas 1917 is a poorly studied and rarely collected taxon of Akodontini (Sigmodontinae). The single described species, Deltamys kempi (DKE), has a basic karyotype with a diploid number of 2n = 37 in males and 2n = 38 in females, a fundamental number FN = 38 for both sexes, and an X(1)X(1)X(2)X(2)/X(1)X(2)Y sex determination system. Herein, a new allopatric form, Deltamys sp. (DSP), is reported, based on specimens from southern Brazil, with 2n = 40, FN = 40 and XX/XY sex chromosomes. We describe the karyotype and mechanism of chromosomal differentiation between both Deltamys complements. Phylogenetic analyses, based on the complete sequence (1,140 bp) of the mitochondrial cytochrome b gene, grouped Deltamys sp. as sister species to D. kempi, with up to 12% genetic divergence between them. The GTG-banding patterns show complete autosomal correspondence between D. kempi and Deltamys sp. and identify a tandem rearrangement involving DSP7, DSP19 and DKE4 that is responsible for the differences in 2n and FN. Chromosome painting with Akodon paranaensis chromosome 21 (a small metacentric akodont marker) paint revealed total homology with the smallest acrocentric Deltamys sp. chromosome, DSP19. This suggests the occurrence of a pericentric inversion or centromeric shift when compared to other akodontines, with a posterior tandem rearrangement giving rise to DKE4. In DKE, large blocks of pericentromeric constitutive heterochromatin are present on the autosomes and the X, and the Y/autosome has an entirely heterochromatic short arm. In DSP, small heterochromatic blocks are observed on autosomes and X, and the Y is a very small, mostly heterochromatic acrocentric. The cytogenetic analyses suggest that the Deltamys sp. karyotype is ancestral, with the derived condition resulting from a tandem fusion (DSP7 + DSP19) and the Y/autosome translocation giving rise to the multiple sex chromosome system. The autosomal rearrangements, the differences in CBG-banding patterns and Ag-NOR localization, as well as the presence of X(1)X(1)X(2)X(2)/X(1)X(2)Y and XX/XY sex determination mechanisms, possibly acting as a reproductive barrier, and the phylogenetic position within the Deltamys genus, with high genetic divergence, call for a taxonomic review of the genus.

Asunto(s)

Cromosomas de los Mamíferos/genética , Citocromos b/genética , Filogenia , Sigmodontinae/genética , Animales , Brasil , Bandeo Cromosómico , Pintura Cromosómica , Diploidia , Evolución Molecular , Femenino , Geografía , Cariotipo , Cariotipificación , Masculino , Cromosomas Sexuales/genética , Sigmodontinae/clasificación , Especificidad de la Especie

RESUMEN

Comparative studies among four species--Akodonazarae (2n = 38), A. lindberghi (2n = 42), A. paranaensis (2n = 44) and A. serrensis (2n = 46)--employing classic cytogenetics (C- and G-bands) and fluorescence in situ hybridization with telomeric (TTAGGG)n sequencesare reported here. Non-telomeric signals in addition to the regular telomeric sites were detected in three species:A. azarae, A. lindberghi and A. serrensis. One interstitial telomeric site (ITS) was observed proximally at the long arm of chromosome 1 of A. azarae. The comparison of G-banding patterns among the species indicated that the ITS was due to a tandem fusion/fission rearrangement. Non-telomeric signals of A. lindberghi and A. serrensis were not related to chromosomal rearrangements; instead, the sequences co-localized with (i) heterochromatic regions of all chromosomes in A. serrensis; (ii) some heterochromatic regions in A. lindberghi, and (iii) both euchromatic and heterochromatic regions in the metacentric pair of A. lindberghi. These exceptional findings revealed that ITS in Akodon can be related to chromosomal rearrangements and repetitive sequences in the constitutive heterochromatin and that the richness of TTAGGG-like sequences in the euchromatin could be hypothesized to be a result of amplification of the referred sequence along the chromosome arms.

Asunto(s)

Cromosomas/genética , Muridae/genética , Secuencias Repetitivas de Ácidos Nucleicos/genética , Animales , Evolución Biológica , Brasil , Cromosomas/ultraestructura , Eucromatina/genética , Eucromatina/ultraestructura , Heterocromatina/genética , Heterocromatina/ultraestructura , Hibridación Fluorescente in Situ , Cariotipificación/veterinaria , Muridae/clasificación , Especificidad de la Especie , Telómero/genética , Telómero/ultraestructura

RESUMEN

In this article we review the existing cytogenetic information on the polymorphic dot-like chromosomes in Trinomys iheringi, the only species in the family Echimyidae harboring them, and provide new data on the frequency, banding properties, meiotic behavior and DNA composition of these minute chromosomes. Since no individuals lacking these chromosomes have hitherto been found, one of the main properties of B chromosomes, i.e. dispensability, has not yet been tested, so that some reasonable doubt might exist on whether they are true B chromosomes. The dot-like chromosomes were also present in the twelve new individuals analyzed, showed intraindividual variation in number, most likely due to mitotic instability during development, failed to show C-bands, showed late-replication, paired among them in meiosis, but not with the large chromosomes, and appeared to be mainly composed of telomeric DNA. These results suggest that these dot-like chromosomes might actually be mitotically unstable micro B chromosomes showing very high frequency in the natural populations thus far analyzed. But, to be confident of this conclusion, individuals lacking the dot-like chromosomes should actively be searched in future research to test their dispensability.

Asunto(s)

Cromosomas/genética , Roedores/genética , Animales , Bandeo Cromosómico/métodos , Femenino , Hibridación Fluorescente in Situ/métodos , Cariotipificación/métodos , Masculino , Metafase/genética

RESUMEN

Established cell lines have long been used for in vitro studies of tumor biology, enabling investigators to control growth conditions and to draw important conclusions about the oncogenic microenvironment. However, gene expression behavior in cultured cells may not always reflect the actual in vivo scenario, and analysis derived from such experiments should take into consideration the existing differences between the two environments. We used suppression subtractive hybridization to study transcriptional changes elicited after oncogene transformation and cell line establishment. We found that transcriptional changes elicited in cultured cell lines are in fact representative of late events, and they do not occur early after oncogene transfection or activation. We also determined that a fraction of the transcriptional changes is oncogene specific, whereas other changes are shared between two or more different oncogenes.

Asunto(s)

Humanos , Oncogenes/genética , Transcripción Genética/genética , Transformación Celular Neoplásica/genética , Northern Blotting , Expresión Génica , Hibridación in Situ , Línea Celular/patología , Células Tumorales Cultivadas , Transformación Celular Neoplásica/patología

RESUMEN

This paper provides new data on chromosomes of Brazilian vampire bats Desmodus rotundus and Diphylla ecaudata. These species were analyzed by GTG, CBG- and CB-DAPI banding, AgNO3/CMA3 sequential staining, base-specific fluorochrome dyes and in situ hybridization with 18S rDNA probe. C-banding (CBG) revealed constitutive heterochromatin in the pericentromeric regions in all autosomes and the X and Y chromosomes appeared entirely heterochromatic in both species. CB-DAPI revealed a coincident banding pattern to that obtained by CBG. Triple staining CMA3/DA/DAPI revealed an R-banding and a weak G-banding pattern in the karyotypes. Sequential AgNO3/CMA3 staining showed a NOR located interstitially on the long arm of pair 8 in D. rotundus and on the short arm of pair 13 in D. ecaudata. FISH with a rDNA probe confirmed the location and number of NORs; a difference neither in intensity nor in size of hybridization signal was detected between homologues for both species.

Asunto(s)

Quirópteros/genética , Cromosomas/química , Colorantes Fluorescentes/química , Genes de ARNr , Animales , Brasil , Centrómero/química , Bandeo Cromosómico , Cromosomas/ultraestructura , Femenino , Fluorescencia , Heterocromatina/genética , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Región Organizadora del Nucléolo/genética , Sensibilidad y Especificidad , Tinción con Nitrato de Plata , Cromosoma X , Cromosoma Y

RESUMEN

In a Brazilian population of the neotropical rodent Akodon montensis we found five sex-reversed XY females. These animals were cytogenetically analyzed by chromosome painting using species-specific DNA probes from the Y chromosome, generated by chromosomal microdissection and subsequent use of the degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR). The results showed a chromosome complement with an apparently normal Y chromosome and an X chromosome carrying a translocation that encompasses a large portion of the Y chromosome (seemingly the entire Y). Ovarian histology suggested that these females are fertile. Amplification of the SRY HMG box sequence by PCR shows that at least one copy of the Sry gene is present in the A. montensis XY females. Based on our findings, we suggest that the breakpoint of the X;Y translocation probably altered an X-linked sex-determining locus (or loci), blocking testicular organogenesis in the XY females. Further studies are necessary to determine the precise location and role of this putative sex-determining chromosomal region. Genetic mechanisms of XY sex reversal in A. montensis populations are discussed.

Asunto(s)

Pintura Cromosómica , Fertilidad/genética , Muridae/genética , Proteínas Nucleares , Factores de Transcripción , Translocación Genética/genética , Cromosoma X/genética , Cromosoma Y/genética , Secuencias de Aminoácidos , Animales , Brasil , Bandeo Cromosómico , Rotura Cromosómica/genética , Sondas de ADN/genética , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Diploidia , Trastornos del Desarrollo Sexual , Femenino , Dosificación de Gen , Heterocromatina/genética , Cariotipificación , Masculino , Ovario/patología , Reacción en Cadena de la Polimerasa , Procesos de Determinación del Sexo , Proteína de la Región Y Determinante del Sexo

RESUMEN

Ten species of small rodents of genus Calomys are found in South America. Three of these ten species are known to occur in Brazil: C. tener, C. laucha and C. expulsus (= C. callosus expulsus). Almost all Calomys karyotypes are made up of acrocentric pairs. In this paper we describe a new karyotype with 2n = 46 (FN = 66), including 11 meta/submetacentric and 11 acrocentric autosomal pairs. This is not related to any described Calomys karyotype. The X chromosome is a medium submetacentric and the Y is a small acrocentric. This new karyotype is briefly compared to karyotype of the sympatric species C. tener (2n = 66, FN = 66). The reduced diploid number and small amount of pericentromeric heterochromatin observed in the biarmed chromosomes that contrasts to large blocks seen in acrocentrics seem to indicate that centric fusion and loss of constitutive heterochromatin have led to the new karyotype. Cytogenetic evidence suggests strongly that a new species with 2n = 46 from Central Brazil should be described in the genus Calomys.

Asunto(s)

Ratones/clasificación , Ratones/genética , Animales , Brasil , Bandeo Cromosómico , Cromosomas/ultraestructura , Diploidia , Femenino , Heterocromatina/ultraestructura , Cariotipificación , Masculino , Factores Sexuales , Cromosoma X/ultraestructura

RESUMEN

The effect of aging on the physiologic responses of renal plasma flow (RPF) and glomerular filtration rate to an acute oral protein load (renal reserve) is a poorly understood process. In this study of 37 healthy human volunteers, distributed among three groups (group 1: n = 13, age range 20-39 years; group 2: n = 13, age range 40-59 years; group 3: n = 11, age range 60-68 years), we evaluated the influence of age on some of the vasoactive systems such as plasma renin activity, urinary kallikrein, plasmatic prokallikrein, plasmatic kallikrein, and plasmatic kininogen on RPF and creatinine clearance (Ccr) in response to an acute oral protein load (1 g/kg body weight). The aging process diminished but did not cease the increments in RPF (group 1: 539.6 vs. 658.9 ml/min/1.73 m(2), p < 0. 001; group 2: 509.0 vs. 570.7 ml/min/ 1.73 m(2), p < 0.001; group 3: 453.9 vs. 506.0 ml/min/ 1.73 m(2), p < 0.001) and Ccr (group 1: 139. 7 vs. 166.5 ml/ min/1.73 m(2), p < 0.001; group 2: 126.6 vs. 142.2 ml/min/1.73 m(2), p < 0.001; group 3: 112.6 vs. 121.4 ml/min/ 1.73 m(2), p < 0.01) after a protein overload. The plasma renin activity did not change after a meat meal. On the other hand, all parameters regarding the kinin system changed significantly in the direction of increased bradykinin formation, despite aging (urinary kallikrein - group 1: 0.25 vs. 0.44 mU/ml, p < 0.005; group 2: 0.25 vs. 0.41 mU/ml, p < 0.005; group 3: 0.33 vs. 0.47 mU/ml, p < 0.005/plasmatic kininogen - group 1: 1.3 vs. 0.9 microg LBK/ml, p < 0.005; group 2: 1.1 vs. 0.7 microg LBK/ml, p < 0.005; group 3: 0.8 vs. 0.7 microg LBK/ml, p < 0.005). These findings indicate that: (1) the aging process narrows but does not cease the increment range in Ccr and RPF after acute oral protein ingestion; (2) increased bradykinin formation plays a definite role in the acute renal vasodilatory response, and (3) contrary to previous clinical studies, our results suggest that the renal reserve is progressively and significantly reduced during the aging process.

Asunto(s)

Envejecimiento/fisiología , Proteínas en la Dieta/administración & dosificación , Sistema Calicreína-Quinina/fisiología , Circulación Renal/fisiología , Adulto , Anciano , Creatinina/metabolismo , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Flujo Plasmático Renal

RESUMEN

We have identified the almost complete correspondence of whole chromosome arms between the karyotypes of Bolomys lasiurus (2n = 33, 34) and Akodon montensis (2n = 24, 25) using comparative analysis of the GTG-banding patterns. To explain the karyotypic differentiation of the species, tandem and centric fusions, pericentric inversions, loss of telomeres and centromeres are required. Localization of telomere sequences using an (TTAGGG)n oligomere as a fluorescence in situ hybridization probe provided evidence of the maintenance of interstitial telomere sequences in a polymorphic centric fusion of recent origin in Bolomys lasiurus. The homeologies shared between the chromosomes of these two species and those of A. cursor (2n = 16), from previous work, are discussed.

Asunto(s)

Bandeo Cromosómico , Evolución Molecular , Muridae/genética , Telómero/genética , Animales , Fusión Artificial Génica , Hibridación Fluorescente in Situ , Cariotipificación , Polimorfismo Genético

RESUMEN

All available published cytogenetic data show the presence of 28 different karyotypes in 311 specimens of A. cursor as an exceptional example of high karyotype variability in a single species. Our present sample of 116 animals collected in the rain forest of the Atlantic coast of the states of São Paulo and Bahia, Brazil, show 25 karyotype constitutions. The diploid number (2n) ranged from 16 to 14, and the number of autosomal arms (NF) from 26 to 18, because of centric fusion and pericentric inversions involving two autosome pairs, pericentric inversions in three other chromosome pairs, trisomy in the pair 7 and the presence of two XO females. Synaptonemal complex analysis, associated with data from experimental cross-breeding, suggested that heterozygous individuals for pericentric inversions have normal fertility. In this paper, we have reviewed the chromosomal data of this species, and have thus standardized the karyotype description and chromosome numbering. We discuss about karyotype evolution of Akodon cursor based on the frequency and constitution of karyotypes of all different geographical samples described so far in the literature.

Asunto(s)

Polimorfismo Genético , Sigmodontinae/genética , Animales , Brasil , Bandeo Cromosómico , Cruzamientos Genéticos , Femenino , Cariotipificación , Masculino , Linaje , Complejo Sinaptonémico

RESUMEN

Akodon cursor is an exceptional example of high chromosomal variability, displaying diploid numbers from 14 to 16 and fundamental numbers (FN) from 18 to 26 as the result of a complex rearrangement in par 1 and pericentric inversions in three autosomal pairs. The difference in the diploid number is due to the presence of a large metacentric pair 1 in the 2n=14 karyotype, a large metacentric 1 and two different submetacentrics (1a and 1b) in 2n=15 and 1a and 1b submetacentric pairs in homozygosis in the 2n = 16 karyotype. Chromosomes 1a and 1b share homology with the short and long arms of the large metacentric 1 respectively. In this paper, evidence based on fluorescence in situ hybridization (FISH) with telomeric sequences and G-banding indicates that pericentric inversions and fusion of chromosomes 1a and 1b are the probable rearrangements giving rise to the large metacentric 1.

Asunto(s)

Arvicolinae/genética , Inversión Cromosómica , Cromosomas/genética , Polimorfismo Genético , Telómero/genética , Animales , Bandeo Cromosómico , Cromosomas/ultraestructura , Femenino , Hibridación Fluorescente in Situ , Cariotipificación , Masculino

RESUMEN

In this cross-over, double-blind study, 12 essential hypertensive patients (stage I, II, and III) with glomerular filtration rate (GFR) between 50 to 80 mL/min/1.73 m2, were submitted to 4 weeks of placebo followed by 12 weeks with isradipine SRO (IS) 5 mg, spirapril (SP) 6 mg, and isradipine plus spirapril (IS + SP). The study evaluated the effects of these drugs on GFR ((99m)Tc DTPA), effective renal plasma flow (ERPF) ((131)I-orthoiodohippurate), urinary sodium excretion (UNaV), urinary kallikrein excretion (UKal), urinary albumin excretion (UAE), and plasma renin activity (PRA). The three protocols significantly reduced mean blood pressure (128 v 107 mm Hg; 126 v 112 mm Hg; 129 v 104 mm Hg with IS, SP and IS + SP, respectively). ERPF and GFR did not change. UNaV increased significantly after IS (0.17 v 0.22 mEq/min) and IS + SP (0.18 v 0.24 mEq/min). UKal increased significantly after IS (58.6%) and IS + SP (53.6%). UAE decreased significantly only after SP. PRA increased significantly after IS (1.31 v 2.84 ng/mL/h), SP (1.10 v 2.15 ng/mL/h), and after IS + SP (1.23 v 3.21 ng/mL/min). In conclusion, IS, SP and IS + SP were effective in reducing blood pressure while keeping renal function stable. Only SP significantly decreased UAE. Enhanced UKal may have played a role in natriuresis observed after IS and IS + SP.

Asunto(s)

Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/administración & dosificación , Enalapril/análogos & derivados , Hipertensión Renal/tratamiento farmacológico , Isradipino/administración & dosificación , Enfermedades Renales , Natriuresis/efectos de los fármacos , Circulación Renal/efectos de los fármacos , Anciano , Albuminuria/inducido químicamente , Estudios Cruzados , Método Doble Ciego , Quimioterapia Combinada , Enalapril/administración & dosificación , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Hipertensión Renal/fisiopatología , Calicreínas/efectos de los fármacos , Calicreínas/orina , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Flujo Plasmático Renal Efectivo/efectos de los fármacos , Método Simple Ciego

RESUMEN

The neotropical rodents Akodon cursor (2n = 14, 15, and 16) and A. montensis (2n = 24 and 25), two closely related and morphologically indistinguishable species, have been compared by G-banding and chromosome painting. In situ hybridization of a biotinylated DOP-PCR product obtained from a microdissected chromosome of A. cursor onto A. montensis chromosomes was performed in combination with localization of telomeric sequences using a (TTAGGG)n oligomer as a FISH probe. The results provide evidence of the complex chromosomal rearrangements suggested by GTG-banding analysis, indicating the origin of one A. cursor autosome from three different A. montensis autosomes. Furthermore, the complete cytogenetic homeology between the A. cursor and A. montensis karyotypes was determined, along with the occurrence of tandem fusions and pericentric inversions and the loss of telomeres, centromeres, and chromosome arms. Evidence for the ancestral origin of the A. cursor karyotype is also provided.

Asunto(s)

Hibridación Fluorescente in Situ/métodos , Roedores/genética , Animales , Centrómero/genética , Bandeo Cromosómico , Biblioteca de Genes , Reordenamiento Génico , Especificidad de la Especie , Telómero/genética

RESUMEN

Fifteen patients with uncomplicated mild to moderate primary hypertension (7 males, 8 females, age range 36-65 years) were submitted to a double blind randomized crossover study, receiving MgO 3 times a day at a daily dose of 1.0 g (600 mg/day of magnesium) and placebo for a period of 6 weeks. This was to test the effects of oral magnesium supplementation on blood pressure and sodium, potassium, calcium and magnesium intraerythrocyte concentrations. Concomitantly, plasma renin activity and serum aldosterone was also measured. Oral magnesium reduced significantly the systolic (delta = -7.6 mmHg, P < 0.05); diastolic (delta = -3.8 mmHg, P < 0.01) and mean blood pressure (delta = -5.9 mmHg, P < 0.01). After magnesium supplementation intraerythrocyte sodium concentration was reduced (delta = -0.55 mEq/l per cell, P < 0.01) and intraerythrocyte magnesium concentration was increased (delta = 1.20 mg/dl per cell, P < 0.01). The diminution of the blood pressure correlated positively with the reduction in intraerythrocyte sodium (r = 0.66, P < 0.01) after magnesium. However, our results have shown that the blood pressure response to oral magnesium was not homogeneous. Forty percent of our patients had their blood pressure effectively controlled (more than 10 mmHg reduction in mean blood pressure), being the hypotensive effect more evident in patients with recent hypertension and in those where the reduction in intraerythrocyte sodium was significantly greater than in the non-responder individuals. Intraerythrocyte potassium and calcium, serum aldosterone, plasma renin activity and urinary sodium excretion were maintained unchanged after magnesium supplementation. These data showed that oral magnesium supplementation may reduce the blood pressure, which can be partially explained by the decrease in intracellular sodium and augment in intracellular magnesium.

Asunto(s)

Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Óxido de Magnesio/uso terapéutico , Magnesio/uso terapéutico , Administración Oral , Adulto , Anciano , Aldosterona/sangre , Antihipertensivos/administración & dosificación , Antihipertensivos/farmacocinética , Brasil , Calcio/farmacocinética , Estudios Cruzados , Método Doble Ciego , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Femenino , Humanos , Magnesio/administración & dosificación , Magnesio/farmacocinética , Óxido de Magnesio/administración & dosificación , Óxido de Magnesio/farmacocinética , Masculino , Persona de Mediana Edad , Placebos , Potasio/farmacocinética , Renina/sangre , Sodio/farmacocinética , Sodio/orina

Asunto(s)

Antihipertensivos/uso terapéutico , Vasos Coronarios/patología , Hipertensión/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Miocardio/patología , Adulto , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Arteriosclerosis/complicaciones , Arteriosclerosis/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/uso terapéutico , Humanos , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/patología , Ratas , Función Ventricular

RESUMEN

PURPOSE: To evaluate the effects of urapidil on blood pressure (BP), renal hemodynamics and lipid and glucose metabolism, in patients with mild-to-moderate uncomplicated essential hypertension. METHODS: Fifteen hypertensive patients, aged 38-64 year-old were studied by ambulatory blood pressure monitoring system (ABPM). It was also evaluated: 1) the creatinine clearance; 2) the effective renal plasma flow by use of a single plasma sample after injection of orthoiodohippurate; 3) the serum triglycerides, cholesterol, and HDL-cholesterol; 4) blood levels of glucose and insulin. The urapidil dose ranged from 60 to 180 mg/day, according to the individual response. RESULTS: The values after four weeks washout-placebo and active treatment with urapidil showed: the systolic/diastolic BP was reduced from 157.7 +/- 6/108.0 +/- 2 on placebo to 140.4 +/- 4/97.3 +/- 3 mmHg (p < 0.05/p < 0.01) after urapidil, respectively, whereas heart rate was unchanged. The percentage of elevated systolic and diastolic BP values during 24h (BP load) was reduced from 60.9% to 54.4% and from 60.8% to 50.3%, respectively. Effective renal plasma flow, glomerular filtration rate, filtration fraction and renal vascular resistance were unaltered by treatment. Significant increase in HDL-cholesterol was observed (from 39.5 +/- 3.6 on placebo vs 49.2 +/- 4.8 mg/dl (p < 0.01) after urapidil. Total cholesterol, LDL-cholesterol and triglycerides levels were not modified with treatment. Circulating plasma glucose and insulin remained unchanged. CONCLUSION: Urapidil is an effective antihypertensive agent without deleterious effect on renal hemodynamics, lipid and glucose metabolism.

Asunto(s)

Antihipertensivos/farmacología , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Hipertensión Renal/fisiopatología , Lípidos/sangre , Piperazinas/farmacología , Adulto , Análisis de Varianza , Antihipertensivos/uso terapéutico , Monitoreo Ambulatorio de la Presión Arterial , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Hipertensión Renal/tratamiento farmacológico , Insulina/sangre , Masculino , Persona de Mediana Edad , Piperazinas/uso terapéutico

Asunto(s)

Endotelio Vascular/fisiología , Hipertensión/fisiopatología , Adulto , Animales , Arginina/farmacología , Presión Sanguínea/efectos de los fármacos , Perros , Endotelinas/sangre , Endotelinas/farmacología , Endotelinas/fisiología , Endotelio Vascular/fisiopatología , Femenino , Humanos , Óxido Nítrico/fisiología , Ratas , Factores de Tiempo

RESUMEN

Most studies that have attempted to distinguish pregnancy-induced hypertension from chronic hypertension in pregnancy include arbitrary clinical definitions and morphological reports based on renal biopsy. To evaluate whether these conditions have different responses to stimuli to the renin-angiotensin-aldosterone system, we studied four normal nonpregnant women, eight normal pregnant women, 10 women with pregnancy-induced hypertension, and 14 with chronic hypertension in pregnancy, in the third trimester of pregnancy, after they had sequentially adopted the supine, the left lateral recumbent, and the orthostatic positions for 90 minutes each. Postural maneuvers did not significantly change mean arterial pressure in pregnancy-induced hypertensive or in normal pregnant women, although in chronic hypertensive women, a significant reduction in this parameter was observed in left lateral recumbency. The renin-angiotensin-aldosterone system was significantly less activated with women in the supine position in pregnancy-induced hypertensive and chronic hypertensive women; however, as opposed to pregnancy-induced hypertensive women, those with chronic hypertension reassumed their humoral response to upright posture, which was accompanied by a significant reduction in sodium excretion. The parallelism between plasma renin activity and aldosterone levels, absent in normal pregnancy, returned in pregnancy-induced hypertensive and chronic hypertensive women in the erect posture (r = 0.73, p less than 0.01; r = 0.68, p less than 0.01, respectively). These data suggest that the adoption of the left lateral recumbent position in pregnancy reduces mean arterial pressure only in chronic hypertensive women. Moreover, in chronic hypertension, the upright position provoked a significant response of the renin-angiotensin-aldosterone system. This effect was not observed in women with pregnancy-induced hypertension.

Asunto(s)

Hipertensión/fisiopatología , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Embarazo/fisiología , Sistema Renina-Angiotensina/fisiología , Adolescente , Adulto , Aldosterona/sangre , Presión Sanguínea , Femenino , Humanos , Hipertensión/sangre , Postura , Embarazo/sangre , Complicaciones Cardiovasculares del Embarazo/sangre , Renina/sangre , Sodio/orina

RESUMEN

The objective of this double-blind, placebo-controlled study was to evaluate the effects of isradipine on renal hemodynamics and function. Ten patients with mild-to-moderate hypertension were given isradipine at 2.5 mg twice daily for 3 months after 4 weeks of placebo washout. Renal studies were performed 2 h after the morning administration of treatment. The results of these evaluations indicate that isradipine as monotherapy significantly reduced the mean arterial pressure, while the effective renal plasma flow was increased (+16%) and glomerular filtration rate remained virtually unchanged (-8.7 ml/min). The filtration fraction and renal vascular resistance decreased significantly. There was a significant decrease in the absolute rate of proximal sodium reabsorption, and a significant increase in the distal reabsorption. Clearance of sodium remained unchanged. In conclusion, monotherapy with low-dose isradipine was not only effective in controlling blood pressure, but also decreased the renal vascular resistance while avoiding glomerular hyperfiltration, and exerted a protective effect on renal hemodynamics. Natriuresis also remained stable despite the blood pressure reduction.

Asunto(s)

Bloqueadores de los Canales de Calcio/efectos adversos , Dihidropiridinas/efectos adversos , Hemodinámica/efectos de los fármacos , Circulación Renal/efectos de los fármacos , Sodio/metabolismo , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/farmacología , Dihidropiridinas/administración & dosificación , Dihidropiridinas/farmacología , Método Doble Ciego , Humanos , Isradipino