Biomedical subjects

Yi Zhang

Publications and source records attributed to Yi Zhang.

At least 217 records · Page 12Linked to original sources

PubMed2005

The controlled evolution of a polymer single crystal.

We present a method for controlling the initiation and kinetics of polymer crystal growth using dip-pen nanolithography and an atomic force microscope tip coated with poly-dl-lysine hydrobromide. Triangular prisms of the polymer epitaxially grow on freshly cleaved mica substrates, and their in-plane and out-of-plane growth rates can be controlled by raster scanning the coated tip across the substrate. Atomic force microscope images were concomitantly recorded, providing a set of photographic images of the process as it spans the nanometer- to micrometer-length scales as a function of environmental conditions.

Aluminum Silicates↗

PubMed2005

Analogues of vaccinia virus DNA topoisomerase I modified at the active site tyrosine.

The mechanism of type IB topoisomerase-mediated DNA relaxation was studied by modification of vaccinia topoisomerase I at the active site tyrosine (position 274) with several tyrosine analogues. These analogues had varied steric, electronic, and stereochemical features to permit assessment of those structural elements required to support topoisomerase function. Eleven tyrosine analogues were successfully incorporated into the active site of vaccinia topoisomerase I. It was found that only tyrosine analogues having the phenolic -OH group in the normal position relative to the protein backbone were active. Modifications that replaced the nucleophilic tyrosine OH (pKa approximately 10.0) group with NH2 (pKa 4.6), SH (pKa approximately 7.0), or I groups or that changed the orientation of the nucleophilic OH group essentially eliminated topoisomerase I function. For the active analogues, the electronic effects and H-bonding characteristics of substituents in the meta-position of the aromatic ring may be important in modulating topoisomerase I function. The pH profile for the functional analogues revealed a small shift toward lower pH when compared with wild-type topoisomerase I.

Amino Acid Sequence↗

PubMed2005

Fold-speed control in collapsing mixed phospholipid monolayers.

Mixed monolayers of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoyl-phosphatidylserine are compressed beyond their collapse pressure. Primary and secondary folds that grow perpendicular to the compression direction are observed using Brewster angle microscopy. The secondary fold velocity is measured with a fast charge-coupled device camera. We observe a reduction in secondary fold speed when increasing the mole fraction of the softer DPPC component in the monolayer. The fracture kinetics follows theoretical predictions for the fold coarsening dynamics of uniaxially stressed three-dimensional systems.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2005

Functional analysis of the human variants of breast cancer resistance protein: I206L, N590Y, and D620N.

Previous studies have shown that the V12M and Q141K variants of breast cancer resistance protein (BCRP) can affect expression and function of the transporter. In this study, the effects of the I206L, N590Y, and D620N variants on protein expression, plasma membrane localization, and transport activity of BCRP were investigated. Wild-type BCRP and the three variants were stably expressed in human embryonic kidney (HEK) cells. Confocal microscopy analysis showed that the three variants were predominantly routed to the plasma membrane of HEK cells. The expression level of I206L in the plasma membrane was approximately 45% of that of wild-type protein, whereas the N590Y and D620N levels were increased approximately 3.6-fold and 2.4-fold, respectively, as determined by immunoblotting. All three variants transported mitoxantrone, pheophorbide a, and BODIPY FL-prazosin. After normalization for differences in BCRP expression, I206L, N590Y, and D620N exhibited approximately 2-fold, 0.3-fold, and 0.5-fold wild-type efflux activities, respectively. The variants also conferred resistance to mitoxantrone and topotecan. Mitoxantrone and topotecan resistance by I206L and N590Y was approximately 2-fold and 0.3-fold of the wild-type BCRP resistance levels, respectively. Although D620N conferred a topotecan resistance similar to that of the wild-type protein, its level of mitoxantrone resistance was decreased by 50%. After normalization to BCRP expression levels, ATPase activities of I206L were not significantly different from those of wild-type protein, whereas N590Y and D620N exhibited approximately 30% and 50% of wild-type ATPase activities, respectively. These results suggest that I206L has the lowest protein expression and the highest activity, whereas N590Y and D620N display higher expression and lower activity, relative to wild-type BCRP.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2005

Alloreactive memory T cells are responsible for the persistence of graft-versus-host disease.

Graft-vs-host disease (GVHD) is caused by a donor T cell anti-host reaction that evolves over several weeks to months, suggesting a requirement for persistent alloreactive T cells. Using the C3H.SW anti-C57BL/6 (B6) mouse model of human GVHD directed against minor histocompatibility Ags, we found that donor CD8(+) T cells secreting high levels of IFN-gamma in GVHD B6 mice receiving C3H.SW naive CD8(+) T cells peaked by day 14, declined by day 28 after transplantation, and persisted thereafter, corresponding to the kinetics of a memory T cell response. Donor CD8(+) T cells recovered on day 42 after allogeneic bone marrow transplantation expressed the phenotype of CD44(high)CD122(high)CD25(low), were able to homeostatically survive in response to IL-2, IL-7, and IL-15 and rapidly proliferated upon restimulation with host dendritic cells. Both allogeneic effector memory (CD44(high)CD62L(low)) and central memory (CD44(high)CD62L(high)) CD8(+) T cells were identified in B6 mice with ongoing GVHD, with effector memory CD8(+) T cells as the dominant (>80%) population. Administration of these allogeneic memory CD8(+) T cells into secondary B6 recipients caused virulent GVHD. A similar allogeneic memory CD4(+) T cell population with the ability to mediate persistent GVHD was also identified in BALB/b mice receiving minor histocompatibility Ag-mismatched B6 T cell-replete bone marrow transplantation. These results indicate that allogeneic memory T cells are generated in vivo during GVH reactions and are able to cause GVHD, resulting in persistent host tissue injury. Thus, in vivo blockade of both alloreactive effector and memory T cell-mediated host tissue injury may prove to be valuable for GVHD prevention and treatment.

Animals↗

PubMed2005

The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitment.

Development of immature T-cell precursors (thymocytes) to either the CD4 helper or CD8 killer T-cell lineages correlates precisely with their T-cell receptor specificity for major histocompatibility complex class II or class I molecules, respectively, indicating that the process is carefully regulated. Although intensively studied owing to its importance in determining the composition of the mature T-cell compartment and as a general model of binary lineage decisions, the underlying molecular pathways remain obscure. We have previously reported a spontaneous mouse mutant (HD (helper deficient) mice) in which lineage commitment is specifically perturbed without affecting positive selection. Here we show that a point mutation in the zinc finger transcription factor Th-POK (T-helper-inducing POZ/Krüppel-like factor) is responsible for redirection of class-II-restricted thymocytes to the CD8 lineage in HD mice. Furthermore, we demonstrate that constitutive expression of this factor during thymic development leads to redirection of class-I-restricted thymocytes to the CD4 lineage, indicating that Th-POK is a master regulator of lineage commitment.

Amino Acid Sequence↗

PubMed2005

Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formation.

It is widely accepted that the familial Parkinson's disease (PD)-linked gene product, parkin, functions as a ubiquitin ligase involved in protein turnover via the ubiquitin-proteasome system. Substrates ubiquitinated by parkin are hence thought to be destined for proteasomal degradation. Because we demonstrated previously that parkin interacts with and ubiquitinates synphilin-1, we initially expected synphilin-1 degradation to be enhanced in the presence of parkin. Contrary to our expectation, we found that synphilin-1 is normally ubiquitinated by parkin in a nonclassical, proteasomal-independent manner that involves lysine 63 (K63)-linked polyubiquitin chain formation. Parkin-mediated degradation of synphilin-1 occurs appreciably only at an unusually high parkin to synphilin-1 expression ratio or when primed for lysine 48 (K48)-linked ubiquitination. In addition we found that parkin-mediated ubiquitination of proteins within Lewy-body-like inclusions formed by the coexpression of synphilin-1, alpha-synuclein, and parkin occurs predominantly via K63 linkages and that the formation of these inclusions is enhanced by K63-linked ubiquitination. Our results suggest that parkin is a dual-function ubiquitin ligase and that K63-linked ubiquitination of synphilin-1 by parkin may be involved in the formation of Lewy body inclusions associated with PD.

Carrier Proteins↗

PubMed2005

Monitoring of anti-vaccine CD4 T cell frequencies in melanoma patients vaccinated with a MAGE-3 protein.

Quantitative evaluation of T cell responses of patients receiving antitumoral vaccination with a protein is difficult because of the large number of possible HLA-peptide combinations that could be targeted by the response. To evaluate the responses of patients vaccinated with protein MAGE-3, we have developed an approach that involves overnight stimulation of blood T cells with autologous dendritic cells loaded with the protein, sorting by flow cytometry of the T cells that produce IFN-gamma, cloning of these cells, and evaluation of the number of T cell clones that secrete IFN-gamma upon stimulation with the Ag. An important criterion is that T cell clones must recognize not only stimulator cells loaded with the protein, but also stimulator cells transduced with the MAGE-3 gene, so as to exclude the T cells that recognize contaminants generated by the protein production system. Using this approach it is possible to measure T cell frequencies as low as 10(-6). We analyzed the frequencies of anti-vaccine CD4 T cells in five metastatic melanoma patients who had been injected with a MAGE-3 protein without adjuvant and showed evidence of tumor regression. Anti-MAGE-3 CD4 T cells were detected in one of the five patients. The frequency of the anti-MAGE-3 CD4 T cells was estimated at 1/60,000 of the CD4 T cells in postvaccination blood samples, representing at least an 80-fold increase in the frequency found before immunization. The frequencies of one anti-MAGE-3 CD4 T cell clonotype were confirmed by PCR analysis on blood lymphocytes. The 13 anti-MAGE-3 clones, which corresponded to five different TCR clonotypes, recognized the same peptide presented by HLA-DR1.

Amino Acid Sequence↗

PubMed2005

Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells.

Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation, have a direct immunosuppressive effect on T-cell proliferation in vitro. However, it is unclear whether they also modulate the immune system by acting on the very first step. In this investigation, we addressed the effects of human MSCs on the differentiation, maturation, and function of dendritic cells (DCs) derived from CD14+ monocytes in vitro. Upon induction with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4), MSC coculture could strongly inhibit the initial differentiation of monocytes to DCs, but this effect is reversible. In particular, such suppression could be recapitulated with no intercellular contact at a higher MSC/monocyte ratio (1:10). Furthermore, mature DCs treated with MSCs were significantly reduced in the expression of CD83, suggesting their skew to immature status. Meanwhile, decreased expression of presentation molecules (HLA-DR and CD1a) and costimulatory molecules (CD80 and CD86) and down-regulated IL-12 secretion were also observed. In consistence, the allostimulatory ability of MSC-treated mature DCs on allogeneic T cells was impaired. In conclusion, our data suggested for the first time that human MSCs could suppress monocyte differentiation into DCs, the most potent antigen-presenting cells (APCs), thus indicating the versatile regulation of MSCs on the ultimate specific immune response.

Cell Differentiation↗

PubMed2005

[Application of endoscopy-assistant operation in surgical treatment of breast diseases].

OBJECTIVE: To explore the technique and problems of endoscope-assistant breast surgery. METHODS: Five patients with breast cancer underwent endoscope-assistant modified radical mastectomy, 30 patients with breast cancer underwent endoscope-assistant modified radical mastectomy with small incision, and 13 patients with breast cancer underwent endoscope-assistant resection of breast cancer with retained breast plus axillary lymph node dissection. Two patients with fibroadenoma and 2 patients with fibrocystic disease breast with atypical hyperplasia were treated with endoscope-assistant subcutaneous total mastectomy and breast reconstruction by one-stage silica gel filling operation. Seven patients with fibrocystic disease with atypical hyperplasia and 16 patients with gynecomastia were treated with endoscope-assistant subcutaneous total mastectomy. One 10-month-old infant with huge chest lymphangioma was treated with endoscope-assistant tumor resection via axilla. RESULTS: All operations were performed smoothly. The duration of operation was 180 approximately 360 min. The frozen sections of skin and breast tissue at the incision margin resected during operation endoscope-assistant modified radical mastectomy with small incision and endoscope-assistant conservative surgery were all negative There were 2 cases of postoperative incisional bleeding, 1 case of skin margin necrosis of axillary incision, 1 case of skin margin incisional necrosis after endoscope-assistant resection of breast cancer with retained breast plus axillary lymph node dissection, 4 cases of epidermal necrosis of nipple, and one case of full thickness skin necrosis of nipple surface. CONCLUSION: Endoscope-assistant breast surgery has changed the routine method in breast operation and manifests the cosmetic effects that cannot be achieved by routine surgery.

Adolescent↗

PubMed2005

Improvements to GALA and dbERGE II: databases featuring genomic sequence alignment, annotation and experimental results.

We describe improvements to two databases that give access to information on genomic sequence similarities, functional elements in DNA and experimental results that demonstrate those functions. GALA, the database of Genome ALignments and Annotations, is now a set of interlinked relational databases for five vertebrate species, human, chimpanzee, mouse, rat and chicken. For each species, GALA records pairwise and multiple sequence alignments, scores derived from those alignments that reflect the likelihood of being under purifying selection or being a regulatory element, and extensive annotations such as genes, gene expression patterns and transcription factor binding sites. The user interface supports simple and complex queries, including operations such as subtraction and intersections as well as clustering and finding elements in proximity to features. dbERGE II, the database of Experimental Results on Gene Expression, contains experimental data from a variety of functional assays. Both databases are now run on the DB2 database management system. Improved hardware and tuning has reduced response times and increased querying capacity, while simplified query interfaces will help direct new users through the querying process. Links are available at http://www.bx.psu.edu/.

Animals↗

PubMed2005

S100A10, annexin A2, and annexin a2 heterotetramer as candidate plasminogen receptors.

The defining characteristic of a tumor cell is its ability to escape the constraints imposed by neighboring cells, invade the surrounding tissue and metastasize to distant sites. This invasive property of tumor cells is dependent on activation of proteinases at the cell surface. The serine proteinase plasmin is one of the key proteinases that participate in the pericellular proteolysis associated with the invasive program of tumor cells. The assembly of plasminogen and tissue plasminogen activator at the endothelial cell surface or on the fibrin clot provides a focal point for plasmin generation and therefore plays an important role in maintaining blood fluidity and promoting fibrinolysis. S100A10, a member of the S100 family of Ca2+-binding proteins, is a dimeric protein composed of two 11 kDa subunits. Typically, S100A10 is found in most cells bound to its annexin A2 ligand as the heterotetrameric (S100A10)2(annexin A2)2 complex, AIIt. In addition to an intracellular distribution, S100A10 is present on the extracellular surface of many cells. The carboxyl-terminal lysines of S100A10 bind tPA and plasminogen resulting in the stimulation of tPA-dependent plasmin production. Carboxypeptidases cleave the carboxyl-terminal lysines of S100A10, resulting in a loss of binding and activity. Plasmin binds to S100A10 at a distinct site and the formation of the S100A10-plasmin complex stimulates plasmin autoproteolysis thereby providing a highly localized transient pulse of plasmin activity at the cell surface. The binding of tPA and plasmin to S100A10 also protects against inhibition by physiological inhibitors, PAI-1 and alpha2-antiplasmin, respectively. S100A10 also colocalizes plasminogen with the uPA-uPAR complex thereby localizing and stimulating uPA-dependent plasmin formation to the surface of cancer cells. The loss of S100A10 from the extracellular surface of cancer cells results in a significant loss in plasmin generation. In addition, S100A10 knock-down cells demonstrate a dramatic loss in extracellular matrix degradation and invasiveness as well as reduced metastasis. Annexin A2 plays an important role in plasminogen regulation by controlling the levels of extracellular S100A10 and by acting as a plasmin reductase. The mechanism by which annexin A2 regulates the extracellular levels of S100A10 is unknown. This review highlights the important part that S100A10 plays in plasmin regulation and the role this protein plays in cancer cell invasiveness and metastasis.

Animals↗

PubMed2005

A polyclonal anti-vaccine CD4 T cell response detected with HLA-DP4 multimers in a melanoma patient vaccinated with MAGE-3.DP4-peptide-pulsed dendritic cells.

During the last few years, HLA class I tetramers have been successfully used to demonstrate anti-vaccine CD8 CTL proliferation in cancer patients vaccinated with tumor antigens. Frequencies of CTL as low as 10(-6) among CD8 cells were observed even in patients showing tumor regression. Little is known about the role of tumor-antigen-specific CD4 T cells in the context of these anti-vaccine responses. Therefore, we developed a very sensitive approach using fluorescent class-II-peptide multimers to detect antigen-specific CD4 T cells in vaccinated cancer patients. We produced HLA-DP4 multimers loaded with the MAGE-3(243-258) peptide and used them to stain ex vivo PBL from melanoma patients injected with dendritic cells pulsed with several class I and class II tumor antigenic peptides, including the MAGE-3(243-258) peptide. The multimer(+) CD4 T cells were sorted and amplified in clonal conditions; specificity was assessed by their ability to secrete IFN-gamma upon contact with the MAGE-3 antigen. We detected frequencies of about 1x10(-6) anti-MAGE-3.DP4 cells among CD4 cells. A detailed analysis of one patient showed an anti-MAGE-3.DP4 CD4 T cell amplification of at least 3000-fold upon immunization. TCR analysis of the clones from this patient demonstrated a polyclonal response against the MAGE-3 peptide.

Antibodies, Neoplasm↗

PubMed2005

In vivo 17O NMR approaches for brain study at high field.

17O is the only stable oxygen isotope that can be detected by NMR. The quadrupolar moment of 17O spin (I = 5/2) can interact with local electric field gradients, resulting in extremely short T1 and T2 relaxation times which are in the range of several milliseconds. One unique NMR property of 17O spin is the independence of 17O relaxation times on the magnetic field strength, and this makes it possible to achieve a large sensitivity gain for in vivo 17O NMR applications at high fields. In vivo 17O NMR has two major applications for studying brain function and cerebral bioenergetics. The first application is to measure the cerebral blood flow (CBF) through monitoring the washout of inert H2 17O tracer in the brain tissue following an intravascular bolus injection of the 17O-labeled water. The second application, perhaps the most important one, is to determine the cerebral metabolic rate of oxygen utilization (CMRO2) through monitoring the dynamic changes of metabolically generated H2 17O from inhaled 17O-labeled oxygen gas in the brain tissue. One great merit of in vivo 17O NMR for the determination of CMRO2 is that only the metabolic H2 17O is detectable. This merit dramatically simplifies both CMRO2 measurement and quantification compared to other established methods. There are two major NMR approaches for monitoring H2 17O in vivo, namely direct approach by using 17O NMR detection (referred as direct in vivo 17O NMR approach) and indirect approach by using 1H NMR detection for measuring the changes in T2- or T1rho-weighted proton NMR signals caused by the 17O-1H scalar coupling and proton chemical exchange (referred as indirect in vivo 17O NMR approach). Both approaches are suitable for CBF measurements. However, recent studies indicated that the direct in vivo 17O NMR approach at high/ultrahigh fields appears to offer significant advantages for quantifying and imaging CMRO2. New developments have further demonstrated the feasibility for establishing a completely noninvasive in vivo 17O NMR approach for imaging CMRO2 in a rat brain during a brief 17O2 inhalation. This approach should be promising for studying the central role of oxidative metabolism in brain function and neurological diseases. Finally, the similar approach could potentially be applied to image CMRO2 noninvasively in human brain.

Animals↗

PubMed2005

Differential protein expression by Porphyromonas gingivalis in response to secreted epithelial cell components.

The human oral pathogen Porphyromonas gingivalis colonizes the gingival crevice and invades gingival epithelial cells. Multidimensional capillary high-performance liquid chromatography coupled with tandem mass spectrometry and two-dimensional gel electrophoresis were used to analyze the proteome of P. gingivalis as it adapts to a set of experimental conditions designed to reflect important features of an epithelial cell environment. 1014 proteins (46% of the total theoretical proteome) were identified in four independent analyses; 479 of these proteins showed evidence of differential expression after exposure of P. gingivalis to either conditioned epithelial cell growth medium or control conditions: i.e., they were only detected under one set of conditions. Moreover, 276 genes annotated as hypothetical were found to encode expressed proteins. Among the proteins up-regulated in the presence of epithelial cell components were a homolog of the internalin proteins of Listeria monocytogenes and subunits of the ATP-dependent Clp protease complex. Insertional inactivation of clpP, encoding the Clp proteolytic subunit, resulted in approximately a 50% reduction in invasion of P. gingivalis. These results suggest that adaptation to an epithelial cell environment induces a major shift in the expressed proteome of the organism. Furthermore, ClpP, that is up-regulated in this environment, is required for optimal invasive activity of P. gingivalis.

Bacterial Adhesion↗

PubMed2005

Mechanisms of depressor effect of norepinephrine injected into subnucleus commissuriu of nucleus solitarius tractus in rabbits.

This experiment aimed to investigate the effect of adrenergic system in the subnucleus commissuriu of nucleus solitrius tractus (CNTS) on renal nerve discharges. Norepinephrine (NE) was microinjected into the CNTS of rabbits and mean arterial blood pressure (MAP) and renal nerve discharges (FRND) were synchronously recorded. The results indicated that (1) microinjection of norepinephine into the CNTS of rabbit could significantly attenuate the frequency of renal nerve discharge, and at the same time decrease markedly the mean arterial pressure. (2) Microinjection of 0.3 nmol yohimbin into CNTS had no significant influence on FRND and MAP, but could attenuate and even reverse the effects of NE on FRND and MAP. These results suggest that microinjection of NE into CNTS may activate the alpha-adrenorecptor located in CNTS and secondarily produce a depressor effect by attenuating the activity of periphenal sympathetic nervous system.

Animals↗

PubMed2005

cDNA expression profiling reveals elevated gene expression in cell clusters overlying focally disrupted myoepithelial cell layers: implications for breast tumor invasion.

BACKGROUND: Our previous studies revealed that a subset of mammary ductal carcinoma in situ (DCIS) contained focally disrupted myoepithelial (ME) cell layers that were predominantly overlain by estrogen receptor (ER) negative cells, which showed a substantially higher rate of cell proliferation and genetic alterations than adjacent ER positive cells within the same duct. This study attempted to assess whether these cells also had a different expression profile on tumor progression related genes. DESIGN: Consecutive sections were made from frozen tissues of 30 DCIS with focally disrupted ME cell layers and associated ER negative cell clusters. ER negative and adjacent ER positive cells within the same duct were microdissected for RNA extraction and amplification. Amplified RNA was converted to biotin-labeled cDNAs and interrogated with 'Cancer PathwayFinder' arrays. RESULTS: Cells within each or among ER negative clusters were immunohistochemically and morphologically similar, whereas they differed substantially from adjacent cells within the same duct. Of 20-paired informative ER negative and positive cells, 15 genes were differentially expressed. Of which, 11(73.3%) were higher in ER negative, 2 (13.3%) were higher in ER positive, and 2 (13.3%) were equal in these cells (p <0.01). Of 11 up-regulated genes in ER negative cells, 8 indirectly or directly promote proliferation and progression, and 3 promote apoptosis. CONCLUSION: ER negative cell clusters showed a significantly higher expressing frequency of multiple tumor progression related genes than their adjacent ER positive counterparts, suggesting that they are likely to be biologically more aggressive and have a greater potential for invasion.

Breast Neoplasms↗

PubMed2005

Apocynin but not allopurinol prevents and reverses adrenocorticotropic hormone-induced hypertension in the rat.

BACKGROUND: Adrenocorticotropic hormone (ACTH)-induced hypertension in the rat is accompanied by increased oxidative stress. This study examines the enzymatic source of reactive oxygen species in ACTH-hypertension. METHODS: Male Sprague-Dawley rats were divided into 10 groups of 10-20 rats per group. The NAD(P)H oxidase inhibitor apocynin (1.5 mmol/L in drinking water) or the xanthine oxidase inhibitor allopurinol (200 mg/kg/day via food) were administered daily. After 4 days, rats were co-administered ACTH (0.2 mg/kg/day) or saline by subcutaneous injection daily for 11 days (prevention study). In a reversal study, ACTH/saline was administered for 13 days and from day 8, apocynin or allopurinol was added for 5 days. Systolic blood pressure (SBP) was measured by the tail-cuff method and oxidative stress using plasma F2-isoprostane concentrations. Results were expressed as mean+/-SEM. RESULTS: ACTH increased SBP (P<.001) but apocynin or allopurinol alone had no effect. Apocynin (but not allopurinol) co-treatment prevented (142+/-3 ACTH, 120+/-4 mm Hg apocynin+ACTH, P'<0.001) and reversed ACTH-induced hypertension (133+/-4 to 118+/-5 mm Hg, P<.05). Plasma F2-isoprostane concentrations were increased in ACTH-treated rats compared with saline (11.9+/-1.0 vs 8.2+/-0.8 nmol/L, P<.01), and apocynin attenuated the ACTH-induced rise in plasma F2-isoprostane concentrations. Serum urate concentrations were undetectable in 75% of rats treated with allopurinol and were not affected by ACTH. CONCLUSIONS: Apocynin but not allopurinol prevented and reversed ACTH-induced hypertension in the rat. These results suggest superoxide production through NAD(P)H oxidase plays a role in ACTH-induced hypertension.

Acetophenones↗