RESUMEN
We generated transgenic mice that expressed a highly expanded 239 polyglutamine (polyQ) repeat under the control of the human androgen receptor promoter. These transgenic mice developed progressive neurological phenotypes of muscular weakness and ataxia, small body size and short life-span. PolyQ nuclear inclusions (NIs) were remarkable and widespread but found in selective regions of the central nervous system (CNS) such as the spinal cord, cerebrum and cerebellum as well as in selective peripheral visceral organs. This distribution pattern resembled that of spinal and bulbar muscular atrophy somewhat, but was more widespread. In neuronal tissues, NIs were present in astrocytes as well as neurons. Cytoplasmic and axonal inclusions were not observed. In the CNS regions with abundant NIs, neuronal populations were well-preserved, and neither neuronal cell death, reactive astrogliosis nor microglial invasions were detected. These findings suggest that polyQ alone can induce the neuronal dysfunction that precedes gross neuronal degeneration and provides a clue for investigating molecular mechanisms that underly the pathway to neuronal dysfunction from polyQ expansion.
Asunto(s)
Degeneración Nerviosa/genética , Péptidos/genética , Receptores Androgénicos/genética , Expansión de Repetición de Trinucleótido , Animales , Muerte Celular , Núcleo Celular/ultraestructura , Humanos , Enfermedad de Huntington/genética , Enfermedad de Huntington/patología , Enfermedad de Huntington/fisiopatología , Cuerpos de Inclusión/genética , Cuerpos de Inclusión/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Trastornos Musculares Atróficos/genética , Degeneración Nerviosa/patología , Degeneración Nerviosa/fisiopatología , Neuronas/patología , Regiones Promotoras Genéticas , Receptores Androgénicos/metabolismo , TransgenesRESUMEN
The cellular distribution of an advanced glycation end product [Nepsilon-(carboxymethyl)lysine (CML)] in aged and Alzheimer's disease (AD) brains was assessed immunohistochemically. CML was localized in the cytoplasm of neurons, astrocytes, and microglia in both aged and AD brains. Glial deposition was far more marked in AD brains than in aged brains, and neuronal deposition was also increased. On electron microscopic immunohistochemistry, neuronal CML formed granular or linear deposits associated with lipofuscin, and glial deposits formed lines around the vacuoles. Neuronal and glial deposits were prominent throughout the cerebral cortex and hippocampus, but were sparse in the putamen, globus pallidus, substantia nigra, and cerebellum, with glial deposits being far more prominent in AD brains. The distribution of neuronal and glial deposits did not correspond with the distribution of AD pathology. The extent of CML deposits was inversely correlated with neurofibrillary tangle formation, particularly in the hippocampus. Most hippocampal pyramidal neurons with neurofibrillary tangles did not have CML, and most of the neurons with heavy CML deposits did not have neurofibrillary tangles. In the hippocampus, neuronal CML was prominent in the region where neuronal loss was mild. These observations suggest that CML deposition does not directly cause neurofibrillary tangle formation or neuronal loss in AD.
Asunto(s)
Envejecimiento/metabolismo , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Lisina/análogos & derivados , Lisina/metabolismo , Neuroglía/metabolismo , Neuronas/metabolismo , Anciano , Anciano de 80 o más Años , Envejecimiento/patología , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Encéfalo/patología , Encéfalo/fisiopatología , Femenino , Humanos , Masculino , Neuroglía/patología , Neuroglía/ultraestructura , Neuronas/patología , Neuronas/ultraestructuraRESUMEN
We report clinical and molecular findings in 15 Japanese mosaic females with r(X) chromosomes, 45,X/46,X,r(X), confirmed by fluorescence in situ hybridization (FISH) analysis for DXZ1 and whole X chromosome painting. Cases 1-3, 5-7, and 11-13 had mental retardation (MR), the remaining cases being free from MR. FISH analysis showed that XIST was absent from the r(X) chromosomes in cases 1-4 and was present on the r(X) chromosomes in cases 5-15. X-inactivation analysis for the methylation status of the AR gene indicated that, of eight cases with XIST-positive r(X) chromosomes in more than 10% (23%-62%) of lymphocytes (cases 5-12), cases 5-10 had selective X-inactivation, whereas cases 11 and 12 had active X disomy. Microsatellite analysis for multiple loci on the pericentromeric region revealed that, of 11 cases with r(X) chromosomes in more than 10% (13%-62%) of lymphocytes (cases 1, 2, and 4-12), cases 1, 2, and 5-10 had heterozygous alleles for at least one locus, whereas cases 4, 11, and 12 had single alleles for all the loci examined. The results suggest that the r(X) and normal X chromosomes could be of biparental or uniparental origin, and that mental status in females with r(X) chromosomes is determined by multiple factors, including the presence or absence of XIST on the r(X) chromosomes and the size and frequency of active r(X) chromosomes, in addition to co-incidental genetic and environmental factors.
Asunto(s)
Discapacidad Intelectual/genética , Mosaicismo/genética , Cromosomas en Anillo , Cromosoma X , Adolescente , Adulto , Pueblo Asiatico/genética , Centrómero/genética , Niño , Preescolar , Mapeo Cromosómico , Femenino , Tamización de Portadores Genéticos , Impresión Genómica , Humanos , Hibridación Fluorescente in Situ , Japón , Cariotipificación , Linfocitos , Masculino , Repeticiones de Microsatélite , LinajeRESUMEN
To clarify the effect of GH on the development of seminiferous tubules in premature male rats, we investigated whether GH accelerates spermatogenesis under the condition of gonadotropin deprivation. Male Wistar rats aged three weeks were divided into three groups and subjected to administration of either long-acting GnRH agonist (GnRHa) or a combination of GnRHa and rat GH, with normal saline solution as control. After the 4-week treatment, sperm density and motility in the right epididymis were measured and seminiferous tubules of right testes were histologically examined. Sperm density and motility were significantly higher in GnRHa+GH-treated rats than in GnRHa-treated rats. In histological examination, the numbers of germ cells in various stages were increased in GnRHa+GH-treated rats compared with GnRHa-treated rats, with the number of mature spermatid being noticeably higher in GnRHa+GH-treated rats. These results suggest that administration of GH decreases loss of germ cells at various stages of spermatogenesis under the condition of gonadotropin withdrawal.
Asunto(s)
Hormona Liberadora de Gonadotropina/agonistas , Gonadotropinas/antagonistas & inhibidores , Hormona del Crecimiento/farmacología , Espermatogénesis/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Análisis de Varianza , Animales , Masculino , Ratas , Ratas Wistar , Recuento de Espermatozoides , Espermatozoides/fisiologíaRESUMEN
Spinal and bulbar muscular atrophy is an X-linked motor neuronopathy caused by the expansion of an unstable CAG repeat in the coding region of the androgen receptor (AR) gene. Nuclear inclusions of the mutant AR protein have been shown to occur in the spinal motor neurons of spinal and bulbar muscular atrophy (Li M, Kobayashi Y, Merry D, Tanaka F, Doyu M, Hashizume Y, Fischbeck KH, Sobue G: Nuclear inclusions in spinal and bulbar muscular atrophy. Ann Neurol 1998 (in press)). In this study, we demonstrate the tissue-specific distribution, immunochemical features, and fine structure of nuclear inclusions of spinal and bulbar muscular atrophy. Nuclear inclusions were observed in affected spinal and brainstem motor neurons, but not in other, nonaffected neural tissues. Similar nuclear inclusions occurred in nonneural tissues including scrotal skin, dermis, kidney, heart, and testis, but not in the spleen, liver, and muscle. These inclusions had similar epitope features detectable by antibodies that recognize a small portion of the N-terminus of the AR protein only, and they were ubiquitinated. Electron microscopic immunohistochemistry showed dense aggregates of AR-positive granular material without limiting membrane, both in the neural and nonneural inclusions. These findings indicate that nuclear inclusions of AR protein are present in selected nonneural tissues as well as in neurons that degenerate in spinal and bulbar muscular atrophy, suggesting that a common mechanism underlies in the formation of neural and nonneural nuclear inclusions.
Asunto(s)
Tronco Encefálico/metabolismo , Parálisis Bulbar Progresiva/metabolismo , Cuerpos de Inclusión/metabolismo , Neuronas Motoras/metabolismo , Atrofia Muscular Espinal/metabolismo , Receptores Androgénicos/metabolismo , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/análisis , Tronco Encefálico/patología , Parálisis Bulbar Progresiva/patología , Núcleo Celular/metabolismo , Núcleo Celular/ultraestructura , Epitelio/metabolismo , Epitelio/patología , Humanos , Técnicas para Inmunoenzimas , Cuerpos de Inclusión/patología , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Masculino , Persona de Mediana Edad , Neuronas Motoras/ultraestructura , Atrofia Muscular Espinal/patología , Miocardio/metabolismo , Miocardio/patología , Especificidad de Órganos , Piel/metabolismo , Piel/patología , Médula Espinal/metabolismo , Médula Espinal/patología , Testículo/metabolismo , Testículo/patologíaRESUMEN
To delineate domains essential for Gq protein coupling in the C-terminal region (C-tail) of rat angiotensin II (Ang II) receptor type 1A (AT1A), we modified the putative cytosolic regions of the receptor by truncation or alanine substitution and determined resultant changes in the guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) effect on Ang II binding and inositol trisphosphate production by the agonist. Independently, we studied the effect of synthetic C-tail peptides (P-5) and its alanine substitution analogs on [35S]GTPgammaS binding to Gq. Effects of GTPgammaS on Ang II binding (shift to a low affinity form) and inositol trisphosphate production in the deletional mutant receptor 1-317 AT1A was similar to wild type AT1A, whereas in shorter C-terminal deletion mutants 1-309, 1-311, 1-312, 1-313 AT1A, and substitutional mutants Y312A, F313A, and L314A these activities were markedly reduced. The binding of [35S]GTPgammaS to Gq was promoted by the synthetic C-terminal peptide P-5 but not when mutated at Tyr312, Phe313, or Leu314. Results indicate that Tyr312, Phe313, and Leu314 in cytosolic carboxyl-terminal region of rat AT1A are essential for coupling and activation of Gq.
Asunto(s)
Angiotensina II/metabolismo , Proteínas de Unión al GTP/metabolismo , Receptores de Angiotensina/metabolismo , Secuencia de Aminoácidos , Animales , Células CHO , Cricetinae , Inositol 1,4,5-Trifosfato/biosíntesis , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Unión Proteica , Ratas , Receptores de Angiotensina/química , Receptores de Angiotensina/genética , Cola (estructura animal)RESUMEN
We examined whether seminiferous tubular function develops normally after discontinuation of long-term gonadal suppression in premature male rats. Wistar male rats 4 weeks old were subjected to the injection of gonadotropin-releasing hormone (Gn-RH) agonist or normal saline solution as control for 12 weeks. The rats were sacrificed 0 and 6 weeks after discontinuation of the treatment. Histological examinations of the seminiferous tubules immediately after cessation of the Gn-RH agonist treatment demonstrated a stage-related change in specific germ cells. Seminiferous tubules of Gn-RH agonist-treated rats were narrow and irregular in shape, and contained significantly fewer spermatids and pachytene spermatocytes at stages VII to XIV than those in controls. A complete development of spermatogenesis was histologically observed 6 weeks after cessation of the treatment. Leydig cells became atrophic without any reduction in cell number immediately after the treatment, but Leydig cells grew rapidly and were similar in appearance to those in control rats 6 weeks after cessation of the treatment. Serum testosterone concentrations were noticeably suppressed immediately after cessation of the treatment (P < 0.01 vs. control) and reached a similar level to those of controls 6 weeks after the cessation. Testes weights were significantly lower in Gn-RH agonist-treated rats than in control rats and had not fully developed 6 weeks after cessation of the treatment (P < 0.01 vs. control). These results suggest that the testicular function develops normally after cessation of the long-term gonadal suppression in premature rats, although the increase in testicular weight may be slightly influenced.
Asunto(s)
Receptores LHRH/agonistas , Túbulos Seminíferos/efectos de los fármacos , Animales , Animales Recién Nacidos , Edad Gestacional , Masculino , Ratas , Ratas Wistar , Espermatogénesis/efectos de los fármacos , Factores de TiempoRESUMEN
Linear focal elastosis in three young Japanese men is described. The lesions are asymptomatic palpable yellow strialike bands extending horizontally across the middle and lower parts of the back. They are histologically composed of many fine wavy bundles of elastic fibers separating the dermal collagen bundles. Electron microscopy demonstrates numerous elongated and fragmented elastic fibers.
Asunto(s)
Enfermedades del Tejido Conjuntivo/patología , Tejido Elástico/ultraestructura , Piel/patología , Adolescente , Adulto , Dorso , Humanos , Masculino , Microscopía ElectrónicaRESUMEN
T4-binding globulin (TBG) is the major transport protein of thyroid hormone in man. Inherited TBG abnormalities were manifested fully in hemizygous males and partially in heterozygous females and transmitted in an X-chromosome-linked fashion, compatible with its location on Xq21-22. We have previously reported that complete deficiency (CD) and partial deficiency (PD) in Japanese subjects resulted from two distinct mutations of the TBG gene, TBG-CDJ and TBG-PDJ, respectively. Recently, we encountered a female manifesting TBG-CD and herein investigated the molecular mechanisms. She was found to possess TBG-CDJ and common-type TBG (TBG-C) alleles by characterizing the TBG gene. Then, X-chromosome inactivation status was evaluated in her family members using a phosphoglycerate kinase (PGK) gene, located on Xq13. Three TBG-CDJ heterozygotes and one unaffected female, confirmed to be PGK heterozygotes for a polymorphic BstXI site, were analyzed. Only the CD female was shown to undergo selective inactivation by examining the BstXI site in amplified products after digestion with a methylation-sensitive enzyme, HpaII. Among an additional eight informative females with TBG deficiency, one heterozygous female for TBG-PDJ shared this selective inactivation pattern. Moreover, the X-chromosome with TBG-C was suggested to be inactivated selectively from the linkage of PGK and TBG alleles recognized in eight of nine family members. Selective X-chromosome inactivation was considered to be the cause of a female heterozygous for TBG-CDJ or -PDJ manifesting the same phenotype as a hemizygote.
Asunto(s)
Proteínas de Unión a Tiroxina/deficiencia , Cromosoma X/fisiología , Secuencia de Bases , Codón , Femenino , Eliminación de Gen , Genes , Genotipo , Heterocigoto , Humanos , Masculino , Biología Molecular , Datos de Secuencia Molecular , Mutación , Sondas de Oligonucleótidos/genética , Linaje , Fenotipo , Fosfoglicerato Quinasa/genética , Proteínas de Unión a Tiroxina/genéticaRESUMEN
Present study was planned to clarify the effects of GH and insulin-like growth factor I (IGF-I) on testosterone secretion using premature male rats. Forty rats were divided four groups. GH, IGF-I, both of them or normal saline solution as control were subcutaneously administered to the rats of each group for seven days from 3-week to 4-week of age. After the treatment, six of each group were used to human chorionic gonadotropin (hCG) loading and four to Leydig cell preparation. Serum testosterone responses to hCG loading were significantly higher in 4-week-old rats treated with GH and/or IGF-I for 1 week than in control rats. However, the responses were similar among three treated groups (GH, IGF-I and both). After one-week treatment with GH and/or IGF-I, isolated Leydig cells were prepared from testes of 4-week-old rats and testosterone production by the stimulation of hCG was examined. Amounts of testosterone production stimulated by hCG were significantly greater in the treated rats than in control rats. These findings suggest that GH mediated by IGF-I promotes the testicular responsiveness to gonadotropin on testosterone production in premature rats.
Asunto(s)
Hormona del Crecimiento/farmacología , Factor I del Crecimiento Similar a la Insulina/farmacología , Células Intersticiales del Testículo/efectos de los fármacos , Testosterona/metabolismo , Análisis de Varianza , Animales , Edad Gestacional , Células Intersticiales del Testículo/metabolismo , Masculino , Ratas , Ratas Wistar , Tasa de Secreción/efectos de los fármacos , Testosterona/biosíntesisRESUMEN
The molecular interaction involved in the ligand binding of the rat angiotensin II receptor (AT1A) was studied by site-directed mutagenesis and receptor model building. The three-dimensional structure of AT1A was constructed on the basis of a multiple amino acid sequence alignment of seven transmembrane domain receptors and angiotensin II receptors and after the beta 2 adrenergic receptor model built on the template of the bacteriorhodopsin structure. These data indicated that there are conserved residues that are actively involved in the receptor-ligand interaction. Eleven conserved residues in AT1, His166, Arg167, Glu173, His183, Glu185, Lys199, Trp253, His256, Phe259, Thr260, and Asp263, were targeted individually for site-directed mutation to Ala. Using COS-7 cells transiently expressing these mutated receptors, we found that the binding of angiotensin II was not affected in three of the mutations in the second extracellular loop, whereas the ligand binding affinity was greatly reduced in mutants Lys199-->Ala, Trp253-->Ala, Phe259-->Ala, Asp263-->Ala, and Arg167-->Ala. These amino acid residues appeared to provide binding sites for Ang II. The molecular modeling provided useful structural information for the peptide hormone receptor AT1A. Binding of EXP985, a nonpeptide angiotensin II antagonist, was found to be involved with Arg167 but not Lys199.
Asunto(s)
Angiotensina II/metabolismo , Modelos Moleculares , Receptores de Angiotensina/química , Secuencia de Aminoácidos , Animales , Sitios de Unión , Células Cultivadas , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Ratas , Receptores de Angiotensina/metabolismoRESUMEN
Angiotensin II receptor type IA (AT1A) has a cysteine (Cys) residue in each of four extracellular domains, and these Cys residues are believed to form two disulfide bridges. However, the question as to which pairs of Cys residues form disulfide bridges have not been experimentally determined. We constructed four mutants of rat AT1A, in which extracellular Cys residues were individually replaced by glycine (mutant C-1, C-2, C-3 and C-4). Further, we constructed two double mutants, in which two extracellular Cys residues were simultaneously substituted for by glycine. The binding affinity for angiotensin II in a double mutant C-1 + 4 (Cys18,274Gly) was similar to that in individually substituted mutants (C-1, C-2, C-3 and C-4) whereas the ligand binding of a double mutant C-2 + 4 (Cys101,274Gly) was completely abolished. The bindings of the non-peptide AT1A antagonist [125I]EXP-985 to mutants C-1, C-4 and C-1 + 4 were only slightly reduced whereas in mutant C-2, C-3 and C-2 + 4 the specific binding for [125I]EXP-985 was completely abolished. These results suggest that disulfide bridges in AT1A are formed between Cys18 and Cys274, and between Cys101 and Cys180, and the latter disulfide bond is essential for the binding of the non-peptidic antagonists [125I]EXP-985 or losartan.
Asunto(s)
Angiotensina II/metabolismo , Disulfuros/química , Receptores de Angiotensina/química , Animales , Unión Competitiva , Compuestos de Bifenilo/metabolismo , Compuestos de Bifenilo/farmacología , Línea Celular , Clonación Molecular , Disulfuros/metabolismo , Ditiotreitol/metabolismo , Ditiotreitol/farmacología , Citometría de Flujo , Imidazoles/metabolismo , Imidazoles/farmacología , Riñón/química , Losartán , Mutagénesis Sitio-Dirigida , Unión Proteica , Ratas , Receptores de Angiotensina/genética , Receptores de Angiotensina/metabolismo , Tetrazoles/metabolismo , Tetrazoles/farmacologíaRESUMEN
To determine the correlation between the types of glycosaminoglycans (GAGs) and the features of rhegmatogenous retinal detachment, we analyzed the types of GAGs in the subretinal fluid of 20 eyes with rhegmatogenous retinal detachment. The GAGs were analyzed by cellulose acetate two-dimensional electrophoresis. Hyaluronic acid alone (HA type) was found in 10 of the 20 eyes. A combination of chondroitin sulfate (chSA) and HA was present (chSA type) in 3 of the 20 eyes. A combination of dermatan sulfate (DS) and HA (DS type) was present in 7 of the 20 eyes. No correlation was found between the type of GAGs and the extent, the duration of detachment, location, size or type of break in the 20 eyes. Some correlation was found between the type of GAGs and the grade of vitreous haze, proliferative vitreoretinopathy (PVR) and the number of surgeries. Retinal detachment with a demarcation line resulted in subretinal strand formation in the DS type eyes, while no such formation was seen in the subretinal space of the eyes of the chSA type. Vitreous haze of grade ( ) was seen in one eye of the DS type, but not seen in the other types. All 3 eyes with PVR of grade C were the DS type. The 2 eyes with reoperated surgeries were the DS type. The presence of DS may indicate an advanced condition of retinal detachment.
Asunto(s)
Exudados y Transudados/química , Glicosaminoglicanos/análisis , Desprendimiento de Retina/complicaciones , Adulto , Anciano , Condroitín/análisis , Dermatán Sulfato/análisis , Electroforesis en Acetato de Celulosa , Humanos , Ácido Hialurónico/análisis , Persona de Mediana Edad , Desprendimiento de Retina/patología , Desprendimiento de Retina/cirugía , Factores de Riesgo , Vitreorretinopatía Proliferativa/etiologíaRESUMEN
To evaluate the effect of cyproterone acetate (CA) on the renin-angiotensin-aldosterone axis, we measured the plasma active, inactive and total renin concentrations (PARC, PIRC and PTRC) during and after CA treatment in patients with precocious puberty and genetic short stature. CA was administered at a daily dose of 150-170 mg/m2 in all subjects. PARC and PTRC were measured by immunoradiometric assays. During CA treatment, PARC, PIRC, PTRC and the PARC/PTRC ratio were significantly decreased. The plasma renin activity, measured by enzymatic assay, and the plasma aldosterone concentration were also decreased. After CA discontinuation, all of these were increased immediately along normal ranges. PARC closely correlated with plasma renin activity. These results suggest that CA produces mineralocorticoid action and suppresses the production and activation of renin.
Asunto(s)
Ciproterona/análogos & derivados , Trastornos del Crecimiento/tratamiento farmacológico , Pubertad Precoz/tratamiento farmacológico , Renina/metabolismo , Antagonistas de Andrógenos/uso terapéutico , Niño , Ciproterona/efectos adversos , Acetato de Ciproterona , Precursores Enzimáticos/metabolismo , Femenino , Trastornos del Crecimiento/genética , Trastornos del Crecimiento/fisiopatología , Humanos , Pubertad Precoz/fisiopatología , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/fisiologíaRESUMEN
Plasma active and inactive renin concentrations (PARC and PIRC) were measured by immunoradiometric assay. Age-related changes in PARC, PIRC and the ratio of PARC/PIRC were studied in 78 normal children, age 1 month to 15 years. The effects of upright position for 15 min were also investigated in 7 postmenarcheal girls. PARC and PIRC in infants were significantly higher than in older children and their ratio of PARC/PIRC was significantly lower than in prepubertal children. During puberty, PARC, PIRC and their ratio were higher in premenarcheal girls than in postmenarcheal girls. In the upright position, PARC, PIRC and the ratio were increased significantly. These finding suggest that: (1) the production of inactive renin is increased but the activation of renin may be lowered in infants; (2) the activation of renin is affected by the menstrual cycle, and (3) the production and activation of renin are increased during short term standing.
Asunto(s)
Renina/sangre , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Ensayo Inmunorradiométrico , Lactante , Recién Nacido , Masculino , Plasma , Pubertad/metabolismo , Factores SexualesRESUMEN
In normal children aged one month to 16 years, the plasma active renin concentration (PARC) was measured with a renin immunoradiometricassay (IRMA) kit, and was compared with plasma renin activity (PRA). The IRMA for renin was found to be independent of the amount of renin substrate and not affected by the dilution of plasma samples, and was therefore proved to be a simple and reliable method. PRA measured in non-diluted plasma samples correlated well with PARC. In the age-related change, PARC in infants was significantly higher than that in older children. In infants, PARC was markedly higher in the crying state than that in the non-crying state. In normal children aged 7 to 11 years, PARC was significantly increased in the upright position compared to the supine position. These findings suggest that a hyperresponse of PARC to acute stress during blood sampling may cause an increase in active renin secretion in infants, and that stimulation by short-term standing may accelerate the activation of inactive renin or the release of active renin.