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Biomedical subjects

Y Du

Publications and source records attributed to Y Du.

At least 127 records · Page 7Linked to original sources
PubMed1998

[The correlation between abusing alcohol and antioxidants, antioxidases].

OBJECTIVE: To study the correlation between abusing alcohol and antioxidants, antioxidases and oxygen free radical reaction. METHODS: We measured spectrophotometrically the plasma vitamin C(P-VC), plasma vitamin E(P-VE), plasma beta-carotene (P-beta-CAR) contents and erythrocyte superoxide dismutase (E-SOD), erythrocyte catalase (E-CAT), erythrocyte glutathione peroxidase (E-GSH-Px) activities in 194 male (40 years old) alcohol abusers and 50 male (40 years old) nondrinkers. RESULTS: The average P-VC, P-VE, P-beta-CAR contents and E-SOD, E-CAT, E-GSH-Px activities of the alcohol abuser group were lower than those of the nondrinker group. The P-VC, P-VE, P-beta-CAR contents and E-SOD, E-CAT, E-GSH-Px activities of the alcohol abusers decreased as the time and quantity of abusing alcohol increased. CONCLUSION: The oxygen free radical reaction in the alcohol abusers was pathologically exacerbated, and the balance between oxidation and antioxidation was serious imbalanced.

Adult↗
PubMed1998

[High performance liquid chromatographic analysis of monosaccharide composition in lacquer polysaccharide from sap of lac tree].

This paper reports the separation and determination of monosaccharide composition in lacquer polysaccharide (LPS) by HPLC. The five monosaccharides were analyzed on microBondapak NH2 column (300 mm x 7.8 mm i.d. 10 microns) and refractive index detection. The mobile phase was CH3CN-H2O-CH3OH (70:25:5, V/V) flowing at a rate of 1.6 mL/min. These monosaccharides were identified by their retention times and quantitatively determined by their peak areas. LPS samples were hydrolysed with 2.0 mol/L CF3COOH. The linear correlation coefficients were all over 0.9953. The average recoveries of monosaccharides ranged 98.8%-103.6% and relative standard deviations were below 5%. The method is simple, rapid, precise, and has been used satisfactorilly for analysis of the monosaccharides hydrolyzed from LPS, which were isolated from sap of three kinds of Lac tree (Maoba Damu, Maoba Xiaomu and Jianshi) in Hubei province.

Chromatography, High Pressure Liquid↗
PubMed1998

[Significance of resistance index and pulsatility index in differential diagnosis of breast neoplasm].

OBJECTIVE: To investigate the significance of the resistance index (RI) and pulsatility index (PI) in differential diagnosis between the benign and malignant breast neoplasms. METHODS: Forty-seven cases of malignant breast tumors, sixty-nine cases of fibroadenomas, seven cases of inflammatory masses and twenty-two cases of mammiplasia were demonstrated on color Doppler flow imaging (CDFI). The measurements of RI and PI of the four groups were recorded respectively and the comparison between benign and malignant neoplasms was made by applying Doppler quantitative analysis. RESULTS: The color flow was detected in 59.4% of benign breast neoplasms and in 89% of malignant ones respectively (chi 2-test, P < 0.001). There were significant difference between benign and malignant neoplasms on the RI and PI. The malignant neoplasms were characteristic of higher RI (> or = 0.70) and PI (> or = 1.30), which were of satisfactory value for differential diagnosis, amounting to 95.5% of accuracy. CONCLUSIONS: Combination of both color Doppler analysis and 2D-US might remarkably increase the sensitivity and specificity of differential diagnosis of breast neoplasms. Our results confirmed the significance of color Doppler flow imaging and Doppler quantitative analysis on the differential diagnosis of breast neoplasms.

Adult↗
PubMed1997

Phosphorylation of steroidogenic acute regulatory protein (StAR) modulates its steroidogenic activity.

Steroidogenic acute regulatory protein (StAR) plays a critical role in steroid hormone synthesis. StAR is thought to increase the delivery of cholesterol to the inner mitochondrial membrane where P450scc resides. Tropic hormones acting through the intermediacy of cAMP rapidly increase pregnenolone synthesis, and this rapid steroidogenic response is believed to be due to StAR's action. The StAR protein contains two consensus sequences for phosphorylation catalyzed by protein kinase A that are conserved across all species in which the amino acid sequence of the StAR protein has been determined. We demonstrated that human StAR expressed in COS-1 cells exists in at least four species detectable by two-dimensional gel electrophoresis followed by Western blotting. The two more acidic species disappeared after treatment of the cell extracts with alkaline phosphatase. 32P was incorporated into StAR protein immunoprecipitated from COS-1 cell extracts, and a 10-min treatment with 8-bromo-cAMP increased 32P incorporation into the StAR preprotein. StAR protein generated by in vitro transcription/translation was phosphorylated by the protein kinase A catalytic subunit in the presence of [gamma-32P]ATP. Mutation of potential sites for protein kinase A-mediated phosphorylation at serine 57 and serine 195 to alanines, individually, reduced 32P incorporation from labeled ATP into StAR preprotein produced by in vitro transcription/translation when incubated with protein kinase A catalytic subunit. 32P labeling of StAR protein expressed in COS-1 cells was also reduced when serine 57 or serine 195 were mutated to alanines. A double mutant in which both serine 57 and serine 195 were changed to alanines displayed markedly reduced 32P incorporation. To determine the functional significance of StAR phosphorylation, we tested the steroidogenic activity of the wild-type StAR and mutated StAR proteins in COS-1 cells expressing the human cholesterol side chain cleavage enzyme system. Mutation of the conserved protein kinase A phosphorylation site at serine 57 had no effect on pregnenolone synthesis. However, mutation of the serine residue at 195 resulted in an approximately 50% reduction in pregnenolone production. The S195A mutant construct did not yield the more acidic species of StAR detected in two-dimensional Western blots, indicating that the mutation affected the ability of the protein to be post-translationally modified. Mutation of the corresponding serine residues in murine StAR (Ser56 and Ser194) to alanines yielded results that were similar to those obtained with human StAR; the S56A mutant displayed a modest reduction in steroidogenic activity, whereas the S194A mutant had approximately 40% of the activity of murine wild-type StAR. In contrast to the human S195A mutation, conversion of serine 195 to an aspartic acid residue had no effect on steroidogenic activity, consistent with the idea that a negative charge at this site modulates StAR function. Our observations suggest that phosphorylation of serine 194/195 increases the biological activity of StAR and that this post- or co-translational event accounts, in part, for the immediate effects of cAMP on steroid production.

Amino Acid Sequence↗
PubMed1997

The Tabby phenotype is caused by mutation in a mouse homologue of the EDA gene that reveals novel mouse and human exons and encodes a protein (ectodysplasin-A) with collagenous domains.

Mouse Tabby (Ta) and X chromosome-linked human EDA share the features of hypoplastic hair, teeth, and eccrine sweat glands. We have cloned the Ta gene and find it to be homologous to the EDA gene. The gene is altered in two Ta alleles with a point mutation or a deletion. The gene is expressed in developing teeth and epidermis; no expression is seen in corresponding tissues from Ta mice. Ta and EDA genes both encode alternatively spliced forms; novel exons now extend the 3' end of the EDA gene. All transcripts recovered have the same 5' exon. The longest Ta cDNA encodes a 391-residue transmembrane protein, ectodysplasin-A, containing 19 Gly-Xaa-Yaa repeats. The isoforms of ectodysplasin-A may correlate with differential roles during embryonic development.

Alternative Splicing↗
PubMed1997

Activation of a caspase 3-related cysteine protease is required for glutamate-mediated apoptosis of cultured cerebellar granule neurons.

Neurotoxicity induced by overstimulation of N-methyl-D-aspartate (NMDA) receptors is due, in part, to a sustained rise in intracellular Ca2+; however, little is known about the ensuing intracellular events that ultimately result in cell death. Here we show that overstimulation of NMDA receptors by relatively low concentrations of glutamate induces apoptosis of cultured cerebellar granule neurons (CGNs) and that CGNs do not require new RNA or protein synthesis. Glutamate-induced apoptosis of CGNs is, however, associated with a concentration- and time-dependent activation of the interleukin 1beta-converting enzyme (ICE)/CED-3-related protease, CPP32/Yama/apopain (now designated caspase 3). Further, the time course of caspase 3 activation after glutamate exposure of CGNs parallels the development of apoptosis. Moreover, glutamate-induced apoptosis of CGNs is almost completely blocked by the selective cell permeable tetrapeptide inhibitor of caspase 3, Ac-DEVD-CHO but not by the ICE (caspase 1) inhibitor, Ac-YVAD-CHO. Western blots of cytosolic extracts from glutamate-exposed CGNs reveal both cleavage of the caspase 3 substrate, poly(ADP-ribose) polymerase, as well as proteolytic processing of pro-caspase 3 to active subunits. Our data demonstrate that glutamate-induced apoptosis of CGNs is mediated by a posttranslational activation of the ICE/CED-3-related cysteine protease caspase 3.

Animals↗
PubMed1997

Proviral integrations at the Evi5 locus disrupt a novel 90 kDa protein with homology to the Tre2 oncogene and cell-cycle regulatory proteins.

Evi5 is a common site of retroviral integration in T-cell lymphomas of AKXD mice. Mapping studies have localized Evi5 to a region approximately 18 kb upstream of another common viral integration site, Gfi1, on mouse chromosome 5 (Liao X, Jenkins NA and Copeland NG, (1995a). J. Virol., 69, 7132-7137). Gfi1 encodes a zinc finger transcription factor involved in interleukin-2 signaling. To determine if Evi5 encodes a gene separate from Gfi1 that might also be involved in T-cell disease, we have searched within the Evi5 locus for novel transcripts. A 6.0 kb transcript was identified in these studies that spans the Evi5 locus and is disrupted by viral integration at Evi5. This transcript is expressed in all embryonic and adult mouse tissues examined. While blast searches indicated that Evi5 is a novel gene, homologies were detected between Evi5 and a known oncogene, Tre2, as well as mammalian and yeast cell cycle regulatory proteins. Evi5 thus encodes a gene separate from Gfi1 that may also be involved in T-cell disease.

Amino Acid Sequence↗
PubMed1997

Cloning and expression of a rat brain interleukin-1beta-converting enzyme (ICE)-related protease (IRP) and its possible role in apoptosis of cultured cerebellar granule neurons.

Several members of the IL-1beta-converting enzyme (ICE) family of proteases recently have been implicated in the intracellular cascade mediating the apoptotic death of various cell types. It is unclear, however, whether ICE-related proteases are involved in apoptosis of mammalian neurons and, if so, how they are activated. Here we report the cloning of an ICE-related protease (IRP) from rat brain, which displays strong sequence identity to human CPP32. In situ hybridization histochemistry reveals that this IRP mRNA is expressed in neuron-enriched regions of the developing and adult rat brain but is profoundly downregulated in the adult (compared with developing) brain. To investigate whether this IRP is involved in the death of neurons in the developing brain, we studied IRP expression in cultured cerebellar granule neurons. In cultured cerebellar granule neurons, reduction of extracellular K+ reliably induces apoptosis and stimulates overexpression of IRP mRNA. The latter is especially prominent 4 hr after switching from high K+ to low K+ medium. The expression of IRP mRNA was maintained at this level for at least 8 hr and was followed by apoptotic death of these neurons. Induction of IRP mRNA and cell death are blocked completely by adding depolarizing concentrations of K+ </=90 min after switching to low K+ medium (i.e., before the commitment point for apoptosis) and partially blocked by brain-derived neurotrophic factor (BDNF), which also partially rescues granule neurons from low K+-induced apoptosis. In addition, overexpression of IRP cDNA in HeLa cells results in cell death accompanied by strong internucleosomal cleavage of DNA, a typical feature of apoptosis. Finally, we detected cleavage of the putative death substrate poly (ADP-ribose) polymerase (PARP), beginning 8 hr after changing from high K+ to low K+ medium, coinciding with the time course of induced expression of the IRP gene. Our data suggest that transcriptional activation of IRP could be one of the mechanisms involved in the apoptotic death of cerebellar granule neurons.

Amino Acid Sequence↗
PubMed1997

Rapid and sensitive detection of Chlamydia trachomatis using a ligatable binary RNA probe and Q beta replicase.

A simple assay format was developed for the direct detection of C. trachomatis rRNA utilizing ligation of recombinant MDV-1 probe RNA fragments hybridized to 23S rRNA after capture and release from a solid support. Assay background (equivalent to 10(4) targets) was suppressed by blocking sequences in the 5' MDV reporter probe fragment complementary to the 3' fragment by prehybridization of a DNA oligonucleotide. A pair of reporter fragments bearing a deletion within the region, obtained by a hydrid-selection-amplification protocol, yielded a low level of assay background which was reduced to < 2% with a blocker directed against the remaining pairing sequence. This probe set showed a sensitivity of 10(3) molecules of 23S rRNA (> 95% responding) and could detect a single elementary body (EB) of Chlamydia trachomatis or 1-10 EB added to a clinical matrix of pooled negative human cervical swab samples. The time of first appearance of amplification products by real-time fluorescence detection showed a linear response to log increases in the target level over a 10(5)-fold range, permitting the determination of target level within an order of magnitude. The assay showed approximately 10(9)-fold discrimination over Chlamydia pneumonae (TWAR) rRNA. High levels of cultured C. albicans, E. coli, S. aureus, or N. gonorrhoeae had no detectable effect on assay background or the ability to detect a single elementary body.

Bacteriological Techniques↗
PubMed1997

Detection of Babesia bovis using a DIG-labeled DNA probe.

A plasmid DNA containing the inserted Babesia bovis cDNA clone designated c51A was used to prepare a DNA probe for B. bovis. The purified 0.6 kb specific DNA fragment was labeled by DIG DNA labeling. After denaturation, the probe was hybridised with the blotted target DNA extracted from bovine red blood cells infected with B. bovis or other protozoa or bovine red blood cells plus extra white blood cells. It was found that the probe produced from purified 0.6 kb DNA fragment could detect sample of B. bovis DNA equivalent to 0.015 microliter of 10% whole infected blood. Compared to the same DNA fragment labeled with photobiotin, this new probe is more sensitive giving a darker hybridization signal, a lighter hybridization background and without any non-specific reactions. These results indicated that this DIG-labeled B. bovis C5lA probe could provide a sensitive and specific method to diagnose clinically suspected B. bovis infections and distinguish B. bovis DNA from other haemoprotozoan infections.

Affinity Labels↗
PubMed1997

The trends in histological types of lung cancer during 1980-1988, Guangzhou, China.

Five thousand five hundred and forty six cases of all lung cancer patients who died during 1980-1988 in Guangzhou, China were investigated retrospectively with a standardized 31-item questionnaire administered to their next of kin. The data of 1093 lung cancer patients(20%, 1093/5546) who had a histological record was analyzed to investigate the changes in histological types and the possible etiologic causes. The difference between the lung cancer deaths with and without histological record is not significant in age, location (peripheral or central) of tumour and status of occupation (P > 0.05), but the difference in sex is significant (P < 0.01). We analyzed the data of 1093 cases by sex and by 3-year period. There had been a shift in the histology pattern with an increase in the percentage of adenocarcinoma (P = 0.0011) and a decrease in percentage of squamous cell carcinoma (P = 0.0027) in males, inversely, there has been an absolute and a relative decrease of percentage in adenocarcinoma in females (P = 0.0028). The percentage of smokers, age of starting to smoke and type of tobacco smoking were nearly constant in both sexes during the studied periods. The pack-years of smoking decreased in males (P = 0.0396), and seemed increase in females (P = 0.1576, no significance). The analysis of occupation and dietary habits among 5546 cases were performed. The proportion of housewives decreased with time (P < 0.001) while the percentage of chemists in females increased (P < 0.001) with time. The dietary habits are changing with an increase in roast food intake for males (P = 0.0055) and in vegetable intake for males (P < 0.0001), females (P < 0.0001), and for patients with lung squamous cell carcinoma and adenocarcinoma in both sexes (P < 0.001). Perhaps the changes in pack-years of smoking may be responsible for the percentage change of lung cancer histological types observed in our study. The role that changes in dietary habits and status of occupations play in the changing trends of lung cancer histological types in our study need further study.

Adenocarcinoma↗
PubMed1997

1H MAS and 1H[23Na] double resonance NMR studies on the modification of surface hydroxyl groups of gamma-alumina by sodium.

The modification of surface hydroxyl groups with sodium in a series of Na2CO3-gamma-Al2O3 catalysts was investigated as a function of both the Na2CO3 loading and the calcination temperature by means of 1H magic angle spinning (MAS) and 1H(23Na) spin-echo double resonance NMR techniques. The 1H NMR experiments revealed that sodium ions are homogeneously distributed over the alumina surface and closely coordinated with the surface hydroxyl groups. In the catalysts calcined at 250 degrees C, the acidic hydroxyl groups (with a chemical shift of 2.0 ppm) are preferentially associated with sodium ions at low Na2CO3 coverages (5 and 10%), while both the acidic and the basic (0 ppm) hydroxyl groups are accessible for sodium ions at high coverages (15 and 20%). The coordination causes a low-field shift of about 2 ppm in the 1H MAS spectra, and a broad signal at 4.5 ppm appears. It is interesting that the 4.5 ppm signal is completely suppressed in the 1H(23Na) MAS experiments, providing direct evidence that a strong interaction exists between adsorbed sodium ions and the surface hydroxyl groups. Increasing the calcination temperature to 450 degrees C results in preferential removal of the acidic hydroxyl groups, and only the most basic hydroxyl groups remain when the calcination temperature is raised to 600 degrees C. This is attributed to the formation of the coordinated species. [formula: see text] which enhances the acidity of the surface hydroxyl groups and prompts their dehydroxylation, especially at high calcination temperature. Correlation of the 1H MAS NMR results and catalytic activity measurements indicates that the basic hydroxyl groups are essential for the carbonyl sulfide hydrolysis reaction.

Aluminum Oxide↗
PubMed1997

Intracellular targeting of exoenzyme S of Pseudomonas aeruginosa via type III-dependent translocation induces phagocytosis resistance, cytotoxicity and disruption of actin microfilaments.

Exoenzyme S (ExoS) is an ADP-ribosyltransferase secreted by the opportunistic pathogen Pseudomonas aeruginosa. The amino-terminal half of ExoS exhibits homology to the YopE cytotoxin of pathogenic Yersinia. Recently, YopE was found to be translocated into the host cell by a bacteria-cell contact-dependent mechanism involving the ysc-encoded type III secretion system. By using an approach in which exoS was expressed in different strains of Yersinia, including secretion and translocation mutants, we could demonstrate that ExoS was secreted and translocated into HeLa cells by a similar mechanism to that described previously for YopE. Similarly to YopE, the presence of ExoS in the host cell elicited a cytotoxic response, correlating with disruption of the actin microfilament structure. A similar cytotoxic response was also induced by a mutated form of ExoS with a more than 2000-fold reduced ADP-ribosyltransferase activity. However, the enzymatically active ExoS elicited a more definite rounding up of the HeLa cells, which also correlated with decreased viability of the cells after prolonged infection compared with cells infected with strains expressing mutated ExoS or YopE. This suggests that ExoS can act through two different mechanisms on the host cell. The expression of ExoS by Yersinia also mediated an anti-phagocytic effect on macrophages. In addition, we present evidence that extracellularly located P. aeruginosa is able to target ExoS into eukaryotic cells. Taken together, our data suggest that P. aeruginosa, by analogy with Yersinia, targets virulence proteins into the eukaryotic cytosol via a type III secretion-dependent mechanism as part of an anti-phagocytic strategy.

ADP Ribose Transferases↗
PubMed1997

Involvement of a caspase-3-like cysteine protease in 1-methyl-4-phenylpyridinium-mediated apoptosis of cultured cerebellar granule neurons.

Exposure of various neuronal cells or cell lines to high concentrations of 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), results in cell death. Recently, it has been reported that low concentrations of MPP+ induce apoptosis in susceptible neurons. We have further characterized MPP+-mediated toxicity of cultured cerebellar granule neurons (CGNs) and found that exposure of CGNs to relatively low concentrations of MPP+ results in apoptosis, whereas higher concentrations result in necrosis. Cotreatment of CGNs with MPP+ and the tetrapeptide inhibitor of caspase-3-like proteases, acetyl-DEVD-CHO, markedly attenuates apoptotic but not necrotic death of these neurons. The more specific inhibitor of caspase-1-like proteases, acetyl-YVAD-CHO, however, was ineffective against MPP+ neurotoxicity. Moreover, cytoplasmic extracts prepared from MPP+-treated CGNs contain markedly increased protease activity that cleaves the caspase-3 substrate acetyl-DEVD-p-nitroaniline. Finally, the cytoplasmic concentration of the apoptogenic protein cytochrome c was increased in a time-dependent fashion in MPP+-treated CGNs before the onset of apoptosis. Our data confirm that the neurotoxicity of MPP+ is due to both necrosis and apoptosis and suggest that the latter is mediated by activation of a caspase-3-like protease.

1-Methyl-4-phenylpyridinium↗
PubMed1997

Regulation of type 1 ANG II receptor in vascular tissue: role of alpha1-adrenoreceptor.

Angiotensin II (ANG II) and norepinephrine (NE) are important regulators of vascular function and structure. Recent studies showed that there are multiple interactions between these two potent vasoconstrictor agents. The present experiment was designed to investigate the effect of NE on the expression of the type 1 ANG II receptor (AT1) in the aorta and cultured vascular smooth muscle cells (VSMC) of rats. Rats were subcutaneously infused with either NE (0.5 microg x kg(-1) x min(-1), n = 6) or the alpha1-adrenoreceptor antagonist prazosin (3.5 microg x kg(-1) x min(-1), n = 6) for 2 wk. Body weight and tail cuff systolic blood pressure were not modified compared with the vehicle control (P > 0.05). Northern blot analysis showed that AT1 mRNA levels in aorta were decreased by 38% in NE-treated rats and increased 117% in prazosin-treated rats (P < 0.05) compared with control. To determine whether NE directly regulates expression of vascular AT1 mRNA and AT1 receptor density, Northern blot analysis and radioligand binding experiments were performed in cultured VSMC. Incubation of VSMC with NE (10(-7) M) led to 44% decrease in AT1 mRNA levels (P < 0.05) and 39% decrease in AT1 receptor density (P < 0.05). Prazosin, but not the alpha2-adrenoreceptor antagonist yohimbine, prevented NE-induced decrease in AT1 mRNA and AT1 receptor density in these cells. Taken together, our results indicate that vascular AT1 gene expression and receptor protein are regulated by ambient NE levels, and NE-induced downregulation of AT1 mRNA and receptor protein is mediated, at least in part, by activating alpha1-adrenoreceptors.

Adrenergic alpha-Agonists↗
PubMed1997

Reduced responsiveness of hypercholesterolemic rabbit aortic smooth muscle cells to nitric oxide.

The response to nitric oxide of intracellular free Ca2+ levels, measured by fura 2 fluorimetry, and cyclic GMP, measured by RIA, was evaluated on smooth muscle cells of the thoracic aorta in primary culture from normal and cholesterol-fed rabbits. Relaxation to acetylcholine and nitric oxide was also determined in isolated rings of aorta. After 10 weeks of high-cholesterol diet, the intact aorta relaxed less to both acetylcholine and nitric oxide. In cultured cells from hypercholesterolemic rabbits, intracellular Ca2+ oscillated, and the mean Ca2+ levels were approximately twofold greater than in normal aortic cells. Nitric oxide failed to affect basal Ca2+ in either cell type. The peak and sustained rise in intracellular Ca2+ induced by angiotensin II (10(-7) mol/L) were similar in the two cell types. However, nitric oxide (10(-10) to 10(-6) mol/L) decreased the sustained Ca2+ levels to a significantly smaller extent in cells from cholesterol-fed rabbits. In addition, in cells from hypercholesterolemic rabbits, nitric oxide added before angiotensin II inhibited to a smaller degree the transient increase in intracellular free Ca2+ caused by angiotensin II in the nominal absence of extracellular Ca2+, as well as the increase in Ca2+ associated with the addition of extracellular Ca2+. Measurements of fura 2 quenching caused by Mn2+ influx confirmed that nitric oxide inhibited the entry of extracellular divalent cations significantly less in cells from hypercholesterolemic rabbits. Basal levels of cyclic GMP were significantly less than normal, and nitric oxide increased levels of cyclic GMP to a significantly smaller degree in cells from cholesterol-fed rabbits. These data indicate a substantial resistance to nitric oxide action in aortic smooth muscle cells of cholesterol-fed rabbits. This observation is consistent with the notion that resistance of smooth muscle cells to nitric oxide contributes to abnormal endothelium-dependent vasodilation during hypercholesterolemia and can play a role in the pathogenesis of atherosclerosis.

Animals↗
PubMed1997

Regulation of growth of the adrenal gland in DOC-salt hypertension. Role of angiotensin II receptor subtypes.

To investigate the role of the renin-angiotensin system in the regulation of adrenal growth in deoxycorticosterone (DOC)-salt hypertensive rats, and the adrenal gene expression of angiotensin AT1 and AT2 receptors, three groups of uninephrectomized rats + DOC pellet + 0.9% NaCl were given water (DOC), losartan (DOC-L), or ramipril (DOC-R) by gavage. Controls had sham surgery and water gavage. Tail-cuff systolic and mean intra-arterial blood pressures were significantly higher in the three DOC groups than in controls and not different among the groups. Adrenal weight of DOC was slightly but not significantly greater than that of controls, while those of DOC-L and DOC-R were greater than that of controls (P < .01). Northern blots showed that AT1 and AT2 gene expression was significantly reduced in DOC (by 33% and 60%), while that of AT1 (but not AT2) was significantly reduced further (versus control and DOC) in DOC-L and DOC-R. There were negative correlations between adrenal weight and AT1 (r = -.80, P < .0001) or AT2 (r = -.60, P < .005). We conclude that DOC-salt hypertension downregulates adrenal AT1 and AT2 gene expression by different mechanisms. Removal of the effects of angiotensin by losartan or ramipril downregulates AT1 further and promotes adrenal growth, indicating the presence of an AT1-mediated growth-inhibitory action of angiotensin II on the adrenal gland. These observations constitute an additional example of a growth-inhibitory role for the AT1 receptor, opposite to its more common growth-promoting actions in other organs and tissues.

Adrenal Glands↗