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J Angulo

Publications and source records attributed to J Angulo.

51 records · Page 3Linked to original sources
PubMed1996

Impairment of endothelium-dependent relaxation by increasing percentages of glycosylated human hemoglobin. Possible mechanisms involved.

High levels of glycosylated human hemoglobin impair nitric oxide-mediated responses. However, the percentage of glycosylation for which this effect is observed and the mechanisms involved are unknown. We tested endothelium-dependent relaxations caused by acetylcholine in rat aortic segments either in control conditions or after preincubation with increasing percentages of glycosylated human hemoglobin. Human hemoglobin (1 and 10 nmol/L) inhibited endothelium-dependent relaxations only when glycosylated at 9% or higher. We evaluated the effect of 14% glycosylated human hemoglobin on acetylcholine-evoked responses in vessels preincubated with scavengers of superoxide anions, hydroxyl radical, or hydrogen peroxide (superoxide dismutase, deferoxamine, and catalase, respectively); with inhibitors of xanthine oxidase, cyclooxygenase, or thromboxane synthase (allopurinol, indomethacin, and dazoxiben, respectively); with blockers of thromboxane A2/prostaglandin H2 or endothelin receptors (SQ 30741 and BQ-123); and with the precursor of nitric oxide synthesis L-arginine. Superoxide dismutase abolished the effect of glycosylated hemoglobin, and the other substances did not have any effect. Glycosylated hemoglobin at 14% did not modify either the vasoconstrictions induced by the blocker of nitric oxide synthase NG-nitro-L-arginine methyl ester or the relaxations evoked in deendothelialized vessels by sodium nitroprusside and 8-bromo-cGMP. However, it inhibited the vasodilations evoked by exogenous nitric oxide. Superoxide dismutase abolished this latter effect. We conclude that the threshold for glycosylated human hemoglobin (Hb A1) to inhibit endothelium-dependent relaxation is 9%. This effect is due to interference with endothelial nitric oxide by means of superoxide anion production.

Acetylcholine↗
PubMed1995

Regulation of angiotensinogen gene expression in the rat forebrain by adrenal steroids and relation to salt appetite.

The renin-angiotensin system (RAS) is present in the brain where it participates in regulation of fluid-electrolyte homeostasis and possibly plays a role in arousal of salt appetite. In the present studies using quantitative in situ hybridization histochemistry we examined the level of the angiotensinogen (ANG) mRNA in the forebrain areas associated with fluid-electrolyte balance in adrenalectomized (ADX) rats and ADX rats supplemented either with selective glucocorticoid type II receptor agonist RU 28362 or with the selective type I receptor agonist, aldosterone (ALDO). RU 28362 and ALDO were administered for 7 days via Alzet 2001 osmotic minipumps at the rates of 10 micrograms/microliters/h and 1 microgram/microliter/h, respectively. Following adrenalectomy, rats were maintained on a standard rat chow, water and 3% NaCl ad lib. In situ hybridization was performed either with a synthetic [33P]- or [32P]-3' end-labeled oligonucleotide probe and the level of ANG mRNA was detected by grain counting over a single cell or by quantitative film autoradiography, respectively. Seven days post ADX the ANG mRNA level in all studied forebrain areas -septum-diagonal band of Broca (SEPT/DBB), the areas immediately adjacent to the organum vasculosum of the lamina terminalis (OVLT), the median preoptic nucleus (MnPO), and the medial preoptic area (mPOA)-of ADX rats decreased by 50-60%. ALDO treatment, which did prevent ADX-induced saline ingestion, did not prevent this decrease. However, supplementation with RU 28362 maintained normal levels of ANG mRNA in all the above regions of the brain. Thus the expression of the ANG gene in the studied areas of rat forebrain is predominantly under the control of the adrenal glucocorticoids via the type II receptor and not regulated by an ALDO dose that stabilizes natriuresis from the kidney.

Adrenal Cortex↗
PubMed1995

Influence of endothelium on cultured vascular smooth muscle cell proliferation.

The endothelium exerts a large influence on the underlying vascular smooth muscle, not only by the release of both contracting and relaxing factors but also by its ability to synthesize a large number of molecules that influence vascular smooth muscle growth. In addition to well-characterized growth promoters or growth inhibitors, some endothelium-derived factors, originally described as vasoactive compounds, seem to possess growth-regulatory properties. The vasoconstrictor endothelin-1 elicited a dose-dependent increase of cultured vascular smooth muscle cell DNA synthesis with a maximal effect of 57 +/- 14% over basal levels, whereas vasodilators such as prostacyclin, sodium nitroprusside, and 8-bromoguanosine 3':5'-cyclic monophosphate reduced DNA synthesis by 19 +/- 5%, 22 +/- 2%, and 31 +/- 3%, respectively. Medium conditioned by cultured bovine aortic endothelial cells markedly stimulated both DNA synthesis and proliferation of smooth muscle cells. When medium was conditioned in the presence of the endothelin-converting enzyme inhibitor phosphoramidon, the mitogenic effect was significantly reduced, thus indicating a role for endothelin in the stimulation of smooth muscle cell growth by endothelial cells. However, when both cell types were maintained in a coculture system, a 13 +/- 2% decrease of DNA synthesis was observed in smooth muscle cultures. The addition of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester, the cyclooxygenase inhibitor indomethacin, or both during the coculture period did not revert the antiproliferative effect of endothelial cells in coculture, thereby indicating it is not likely due to these unstable endothelium-derived vasorelaxant molecules.

Animals↗
PubMed1994

Glucocorticoid regulation of mRNA encoding (Na+K) ATPase alpha 3 and beta 1 subunits in rat brain measured by in situ hybridization.

The effect of glucocorticoids on (Na+K)ATPase mRNA synthesis was studied in 19 brain areas of adrenalectomized (ADX) rats untreated or receiving dexamethasone (DEX). For in situ hybridization, we employed a [35S]oligonucleotide probe for the alpha 3-subunit isoform, and a [3H]cDNA coding for the beta 1-subunit of the enzyme. Mean levels of grain density for the alpha 3 subunit mRNA of DEX-treated rats were significantly higher by a 't' test in medial septum, amygdala lateralis (AL) and medialis (AME), gyrus dentatus, CA4 hippocampal area, substantia nigra and periventricular gray, compared to untreated rats. For the beta 1-subunit, mean levels after DEX were significantly higher in AL and lateral preoptic area. In addition, the Kolmogorov-Smirnov test applied to frequency histograms of neuronal densities indicated a coordinate increase in alpha 3 and beta 1-subunit mRNA expression for the CA2 subfield and preoptic area medialis (POA MED). We conclude that (1) glucocorticoids are positive modulators of (Na+K)ATPase mRNA; (2) analysis of frequency histograms suggests that glucocorticoids promote in a few regions (AL, POA MED, CA2 subfield) a coordinate increase in the biosynthesis of the alpha 3 and beta 1-subunit mRNA. In 11 other areas stimulation occurs for one subunit mRNA only, whereas 5 areas were insensitive to glucocorticoid effects on this enzyme.

Adrenal Glands↗
PubMed1994

Pressure-induced contraction of the juxtamedullary afferent arterioles in spontaneously hypertensive rats.

1. In the SHR juxtamedullary nephron preparation, the increase of the perfusion pressure from 80 to 160 mmHg increased the diameters of arcuate arteries but produced a pressure-dependent contraction of the afferent arterioles, a response that can account for renal autoregulation. 2. The pressure-induced contractions of the afferent arterioles were abolished by 1 microM nifedipine and by 10 microM furosemide, suggesting that the autoregulatory responses are mainly mediated by tubuloglomerular mechanisms and can be abolished by calcium antagonists.

Animals↗
PubMed1994

Dexamethasone increases adrenalectomy-depressed Na+,K(+)-ATPase mRNA and ouabain binding in spinal cord ventral horn.

The Na+,K(+)-ATPase plays a key role in the regulation of ion fluxes and membrane repolarization in the CNS. We have studied glucocorticoid effects on biosynthesis of the Na+,K(+)-ATPase and on ouabain binding in the ventral horn of the spinal cord using intact rats, adrenalectomized (ADX) rats, and ADX rats receiving dexamethasone (ADX+DEX) during 4 days. Cryostat sections from spinal cords were incubated with a 35S-oligonucleotide coding for the alpha 3-subunit or a 3H-cDNA coding for the beta 1-subunit of the Na+,K(+)-ATPase using in situ hybridization techniques. In ventral horn motoneurons, grain density per cell and grain density per area of soma for both probes were slightly reduced in ADX rats but significantly increased in the ADX+DEX group, using ANOVA and the Bonferroni's test. Statistical analysis of frequency histograms of neuronal densities further indicated a significant shift to the right for intact rats compared with ADX rats for both probes. Concomitantly, [3H]ouabain binding to membrane preparations from ventral horns was reduced in ADX rats and restored to normal by DEX administration. No effect of adrenalectomy or DEX treatment was obtained in the dorsal horn. In conclusion, glucocorticoids positively modulate the mRNA for the alpha 3-subunit and the beta 1-subunit of the Na+,K(+)-ATPase and recover ouabain binding to normal values. The increments of the synthesis and activity of an enzyme affecting membrane repolarization and synaptic neurotransmission are consistent with the alleged stimulatory effect of glucocorticoids on spinal cord function.

Adrenalectomy↗
PubMed1993

Identification of a Kin nuclear protein immunologically related to RecA protein in the rat CNS.

A polypeptide, called Kin, has been identified in cells of the central nervous system (CNS) by using antibodies raised against RecA protein of E. coli and by in situ hybridization with identified cDNA. RecA protein is a recombination enzyme associated with DNA repair. The RecA cross-reacting polypeptide was immunocytochemically demonstrated in the nuclei of various cells of adult rats. Following Western blot analysis using anti-RecA antibodies, the Kin protein showed a band with an apparent molecular weight of 41 kDa. Double labelling experiments, using in situ hybridization of Kin-17 mRNA with serotonin immunocytochemistry, demonstrated a cytoplasmic distribution of radiolabelling indicating the translation of this messenger RNA in serotonergic neurons. These data indicate the presence of a Kin nuclear protein in the CNS and suggest that neurons may possess some DNA-repair pathways analogous to those described in bacteria.

Animals↗
PubMed1992

Implantation of genetically modified mesencephalic fetal cells into the rat striatum.

Transplantation of dopamine (DA) cells into the rat model of hemiparkinsonism induced by intranigral 6-hydroxydopamine (6-OHDA) injections has so far focused mainly on DA replacement via a pump-like mechanism. In the present study, we employed a model of hemiparkinsonism that uses an intrastriatal approach to lesioning the nigrostriatal DA pathway to assess the possibility of using cell transplantation to cause regeneration of that system. Toward that end, we transplanted two types of cells on the side of the 6-OHDA-induced lesions: 1) nonmodified fetal mesencephalic cells and 2) fetal mesencephalic cells that have been infected with a retrovirus vector containing a PKC beta 1 cDNA. Both types of cells cause behavioral improvement although the changes were more prominent and occurred earlier in the PKC-modified groups. Tyrosine hydroxylase (TH) immunocytochemistry revealed significantly cell survival in both groups of animals; in situ hybridization studies confirmed the continuous expression of TH mRNA in both groups. Interestingly, long TH-positive axons were observed only in the striata of animals implanted with PKC-modified cells. More importantly, surviving endogenous nigral TH-positive cell bodies were found only on the lesioned side in the latter group. The observations in these animals were associated with significantly smaller decreases in [3H]mazindol-labeled DA uptake sites in both the striata and substantia nigra pars compacta on the side ipsilateral to the 6-OHDA-induced lesions. Furthermore, immunohistochemical studies revealed increased gliosis in the striata of animals grafted with the PKC-modified cells. When taken together, these results indicate that transplantation of normal fetal mesencephalic cells can cause behavioral improvement by providing DA to the host striata whereas PKC-modified cells can, in addition, prevent the progressive degeneration of or cause regeneration of the dying nigrostriatal DA neurons in this model of hemiparkinsonism. These results are discussed in terms of their support for a role for second messenger systems and glial cells, as well as extracellular matrix molecules in the regeneration of the CNS.

Amphetamine↗
PubMed1989

Expression of salt hunger in hypophysectomized rats.

Hypophysectomized and pituitary-intact rats were tested for their expression of salt hunger under a variety of experimental conditions. The results show that hypophysectomized rats ingest less salt in response to salt hunger induced by sodium depletion, captopril or angiotensin in comparison to pituitary-intact rats. In contrast, both groups ingest the same amount of salt in response to mineralocorticoid-induced salt hunger. While sodium excretion and plasma sodium levels were comparable in the two groups, the angiotensinogen mRNA was reduced by hypophysectomy in several limbic brain regions as well as in the liver. These results suggest that reduced salt intake in response to manipulations of the body sodium and renin-angiotensin system in hypophysectomized rats may result from decreased angiotensinogen mRNA levels.

Angiotensin II↗
PubMed1989

[Conservative treatment of urethral stenosis in childhood].

During a 19 years period (1969-March 1988) 22 children presented for treatment of urethral strictures. The patients ranged in age from neonatal period to 13 years old, 20 of them were boys and 2 girls. We have found 3 congenital cases, 5 traumatic cases, 9 inflammatory (versus infections) cases and 5 iatrogenic cases. Diagnosis can be suspected from the history and physical examination (voided stream), and confirmed radiographically and endoscopically; we have employed urodynamics studies in 2 cases, and those have seem of much important the follow-up. Treatment is controversial between different authors. In ours series progressive dilatation procedure have been elective (retrograde swelling catheter versus anterograde swelling catheter with cytostomy), with 86.3% of good results.

Adolescent↗
PubMed1986

Sensitization of the Escherichia coli cyclic AMP receptor protein to trypsin cleavage by polydeoxyribonucleotides and polyribonucleotides.

In the absence of cAMP the cyclic AMP receptor protein (CRP) is relatively resistant to trypsin whereas the cAMP X CRP complex is attacked yielding N-terminal core fragments of 14,300 and 18,500 Da which still bind cAMP. The DNA X CRP complex formed at low ionic strength in the absence of cAMP is cleaved by trypsin with the formation of 9,700- and 6,000-Da fragments and the concomitant loss of cAMP binding activity. DNA X CRP remains as resistant to attack by subtilisin, clostripain, and the Staphylococcus aureus V8 protease as unliganded CRP but is slowly digested by chymotrypsin. All of the double-stranded polydeoxyribonucleotides and several of the single-stranded polydeoxyribonucleotides and polyribonucleotides tested render CRP sensitive to cleavage by trypsin. CRP is less rapidly cleaved by trypsin in the presence of d(A)n, d(I)n, and r(C)n indicative of a weaker affinity of CRP for these polynucleotides. The 9,700-Da fragment is N-terminal in CRP and probably terminates at Lys-89. The loss of cAMP binding activity following trypsin cleavage of DNA X CRP indicates that regions beyond this residue are important in the function of the cAMP-binding domain of CRP. The 6,000-Da fragment extends from Val-131 to Arg-185 or Lys-188 and contains part of the F helix involved in DNA binding by CRP.

Amino Acid Sequence↗
PubMed1980

Measurement of the type A behavior pattern in children: assessment of children's competitiveness, impatience-anger, and aggression.

The results of a program of research designed to produce an adequate measure of the type A behavior pattern in children are reported. The type A pattern is a risk factor for heart disease in adulthood and is characterized by extremes of competitiveness, impatience, easily aroused anger, and aggression. A questionnaire called the Matthews Youth Test for Health (MYTH-Form O) contains 17 statements that characterize pattern A behaviors in children. Study 1 was conducted to provide psychometric data for the MYTH. Teachers rated how well these statements characterized 485 children enrolled in grades K, 2, 4 and 6. Those children remaining in the school district 3 months later (N = 420) were rated again. Statistical analyses of these ratings suggest that the MYTH-Form O is a reliable, internally consistent instrument, which yields 2 orthogonal factors: competitiveness and impatience-aggression. As expected, there were substantial gender differences in children's type A behavior. Study 2 tested the construct validity of the MYTH in a subsample of children who were challenged to win a car race against an experimenter; were given an opportunity to play with a variety of toys, including a plastic Bobo doll; and were asked to execute a frustrating task during 1 session. Results showed that type A's won a race against a female (not a male) experimenter by a larger margin than did type B's. Type A's aggressed against a Bobo doll earlier and were more impatient than were type B's throughout the session. These impatient behaviors exhibited by child type A's are similar to those exhibited by adult type A's during the standardized adult type A interview. In sum, these data are supportive of the reliability and validity of the MYTH and represent a first step in the development of an instrument to assess pattern A in elementary school-aged children.

Aggression↗
PubMedDate not supplied

Prevention of endothelial dysfunction in streptozotocin-induced diabetic rats by gliclazide treatment.

The aim of the present work was to analyze whether the oral hypoglycemic drug gliclazide affects diabetic endothelial dysfunction in streptozotocin-induced diabetic rats. Gliclazide was compared with glibenclamide, ascorbic acid, and aminoguanidine. An insulin-dependent model of diabetes was selected to exclude insulin-releasing effects of the drugs. Both in isolated aortic segments and mesenteric microvessels, endothelium-dependent relaxation evoked by acetylcholine (ACh, 1 nM to 10 microM) was significantly reduced in vessels from diabetic animals. This impairment was reversed when the segments were previously incubated with 100 U/ml superoxide dismutase. When streptozotocin-induced diabetic rats were orally treated from the time of diabetes induction with gliclazide (10 mg/kg) or ascorbic acid (250 mg/kg), ACh-induced endothelium-dependent relaxation was well preserved both in aortic segments and mesenteric microvessels. In addition, the impaired vasodilatation to exogenous nitric oxide (NO) in aortic segments was also improved in gliclazide-treated diabetic rats. On the other hand, oral treatment with glibenclamide (1 and 10 mg/kg) or aminoguanidine (250 mg/kg) did not produce significant improvements in diabetic endothelial dysfunction. We conclude that gliclazide reverses the endothelial dysfunction associated with diabetes. This effect appears to be due not to the metabolic actions of the drug but rather to its antioxidant properties, as it can be mimicked by other antioxidants. We propose that the mechanism involved is the inactivation of reactive oxygen species, which are increased in diabetes probably as a result of increased early protein glycosylation products, such as glycosylated hemoglobin (HbA(1c)). These effects of gliclazide are not shared by other oral hypoglycemic agent such as glibenclamide, or by blockade of advanced glycosylation end product (AGE) generation with aminoguanidine.

Acetylcholine↗
PubMedDate not supplied

Correction of glycosylated oxyhemoglobin-induced impairment of endothelium-dependent vasodilatation by gliclazide.

We have investigated whether gliclazide, a second-generation sulfonylurea hypoglycemic agent, interferes with the impairment of endothelium-dependent nitric-oxide-mediated relaxation produced by 14%-glycosylated human oxyhemoglobin (GHHb). For comparative purposes, other agents, like glibenclamide, aminoguanidine, ascorbic acid or superoxide dismutase (SOD), were also tested. GHHb (10 nM) caused a reduction in endothelium-dependent relaxation induced by acetylcholine (1 nM to 10 microM) in both isolated aortic segments and mesenteric microvessels from normoglycemic nondiabetic rats. Preincubation of the vessels with gliclazide (100 nM to 10 microM) prevented the impairment of endothelial relaxation, the threshold concentration of gliclazide being 300 nM. In addition, 10 microM gliclazide also prevented the reduction by 10 nM GHHb of the relaxation induced by exogenous nitric oxide (NO, 10 nM to 100 microM). Determination of superoxide anion release measured by the reduction in ferricytochrome c indicated that GHHb produced significant amounts of these free radicals that were concentration-dependently inhibited by gliclazide. The impairment of endothelium-mediated responses was also prevented by 100 U/ml SOD or 10 microM ascorbic acid, but not by 10 microM glibenclamide or 100 microM aminoguanidine. We conclude that gliclazide can reduce the impairment of nitric-oxide-mediated endothelium-dependent relaxation produced by GHHb. This reduction is likely related to the antioxidant properties of the drug, a mechanism suggested by these studies which demonstrate the inactivation of superoxide anions produced by the glycosylated protein by gliclazide.

Acetylcholine↗