Biomedical subjects

D Sun

Publications and source records attributed to D Sun.

At least 289 records · Page 16Linked to original sources

PubMed1995

Determination of the structural role of the internal guanine-cytosine base pair in recognition of a seven-base-pair sequence cross-linked by bizelesin.

Bizelesin (formerly U77,779, The Upjohn Co.) is a bifunctional DNA cross-linking antitumor antibiotic consisting of two open-ring homologs of the (+)-CC-1065 cyclopropa[c]pyrrolo[3,2-e]indol-4(5H)-one (CPI) subunits connected by a rigid linking moiety. Previous studies have shown that Bizelesin most often forms an interstrand cross-link through the N3 of two adenines 6 base pairs (bp) apart (inclusive of the modified adenines). However, gel electrophoresis studies have also indicated that Bizelesin forms 7-bp cross-links in specific sequences. In most of these sequences the cross-linked adenines represent the only possible cross-link site (i.e., no 6-bp site is available); however, in several sequences, a 7-bp sequence is selected in overwhelming preference to a possible 6-bp sequence. In this study, we demonstrate the unique requirement for a G.C base pair within this sequence and the critical presence of the exocyclic 2-amino group of guanine. In a subsequent two-dimensional 1H-NMR study that concentrates on the 7-bp cross-link formed with the sequence 5'-TTAGTTA-3', the role of the central G.C base pairs in the formation of a 7-bp cross-link is probed. 1H-NMR analysis coupled with restrained molecular dynamics (rMD) provides evidence for distortion around the covalently modified adenines. Because of this distortion, the modified bases are twisted toward the center of the duplex adduct, effectively reducing the cross-linked distance. The rMD study also indicates that a hydrogen bond is formed between the exocyclic amine of the central guanine and the carbonyl of the ureylene linker. On the basis of the observation of the distortion in the duplex and the hydrogen bonding between the drug and DNA, it is possible to speculate on the role of the central G.C bases in this sequence preference and propose a mechanism by which Bizelesin forms a 7-bp rather than a 6-bp cross-link with this sequence.

Alkylation↗

PubMed1995

A comparative study of experimental autoimmune encephalomyelitis in Lewis and DA rats.

We compared the T cell responses of Lewis (LEW) and DA rats to guinea pig myelin basic protein (MBP), the synthetic peptides corresponding to the epitopes that are encephalitogenic in the LEW strain (MBP73-86, MBP68-86, and MBP87-99), and bovine proteolipid protein (PLP). DA and LEW rats were susceptible to experimental autoimmune encephalomyelitis (EAE) induced with MBP or MBP68-86, but the peptide was less active in DA rats than in intact MBP molecule. MBP73-86 and MBP87-99 induced EAE in LEW rats but not in the DA strain. MBP89-169 was also encephalitogenic in DA rats. Encephalitogenic CDa+ T cell lines and clones derived from MBP-sensitized DA rats secreted IFN-gamma and TNF-alpha and proliferated to MBP and MBP89-169, but not to MBP68-88. However, T cells from MBP68-86-sensitized DA or LEW rats proliferated specifically in an I-A-restricted response to MBP68-86. T cells from MBP87-99-immunized LEW rats responded to MBP87-99 in the context of I-E, whereas the peptide-specific response of MBP87-99 immunized DA rats was I-A-restricted, although FACScan analysis indicated that DA rats express both I-A and I-E. DA rats were also highly susceptible to EAE induced with PLP; 0.6 nmol was Encephalitogenic for DA rats, but did not induce clinical EAE in LEW rats. Although both DA and LEW rats are highly susceptible to EAE, we demonstrate marked differences in the array of myelin epitopes capable of inducing the disease, as well as the MHC restriction of these epitopes, between the two rat strains.

Animals↗

PubMed1995

Megakaryocyte growth and development factor ameliorates carboplatin-induced thrombocytopenia in mice.

Megakaryocyte growth and development factor (MGDF) administered intraperitoneally (IP) to mice causes a dose-dependent thrombocytosis accompanied by a decrease in mean platelet volume. MGDF increases the number of megakaryocytes in the bone marrow and spleen. MGDF does not affect the circulating number of leukocytes. Carboplatin, a chemotherapeutic agent that causes thrombocytopenia in humans, administered to mice as a single IP injection at a nonlethal dose causes a significant, but reversible thrombocytopenia. The carboplatin-induced thrombocytopenia is accompanied by an increase in circulating endogenous MGDF that precedes the return of circulating platelets to a normal level. MGDF mRNA is constitutively present in the liver. After carboplatin treatment, hepatic MGDF mRNA does not increase in concordance with circulating MGDF. Circulating soluble MGDF receptor levels (c-mpl) do not change significantly during the course of carboplatin-induced thrombocytopenia. MGDF injected IP once daily beginning 1 day after injection of carboplatin reverses carboplatin-induced thrombocytopenia in a dose-dependent fashion. The normalization of circulating platelet numbers in carboplatin plus MGDF-treated mice is accompanied by a normalization of megakaryocyte numbers in the bone marrow. In conclusion, MGDF, by increasing the number of marrow megakaryocytes and circulating platelets is an effective therapy for carboplatin-induced thrombocytopenia in mice.

Animals↗

PubMed1995

Differentially expressed genes in TGF-beta 1 sensitive and resistant human hepatoma cells.

The pathway of growth inhibitory cellular signal transduction by transforming growth factor beta 1 is largely unknown. Although several cellular proteins have been shown to be involved in the pathway, others remain to be identified. To search for other involved proteins, differentially expressed genes were examined in two human hepatoma cell lines that were respectively sensitive and resistant to growth inhibition by TGF-beta 1. Two such genes (SB31 and SB16) were characterized and found to be 100% homologous to leucine-rich alpha 2-glycoprotein and the ribosomal protein S25, respectively. SB31 was coordinately expressed with the TGF-beta I type II receptor, implicating a possible interaction. Expression of both genes in different cell lines can be broadly correlated with the sensitivity of the cell lines to growth inhibition by TGF-beta 1. SB16 expression is strongly suppressed in rat liver regeneration after partial hepatectomy, suggesting that it may have a role in liver growth.

Animals↗

PubMed1995

Self-assembly of a quinobenzoxazine-Mg2+ complex on DNA: a new paradigm for the structure of a drug-DNA complex and implications for the structure of the quinolone bacterial gyrase-DNA complex.

The quinobenzoxazine compounds A-62176 and A-85226 belong to a novel class of antineoplastic agents that are catalytic inhibitors of topoisomerase II and also structural analogs of the antibacterial DNA gyrase inhibitor Norfloxacin. In vitro studies have shown that their antineoplastic activity is dependent upon the presence of divalent metal ions such as Mg2+ and Mn2+, although the precise role of these ions in the mechanism of action is unknown. In this study we have investigated the structures of the binary complex between the quinobenzoxazines and Mg2+ and the ternary complex between quinobenzoxazine-Mg2+ and DNA. The stoichiometry of the binary and ternary complexes and the biophysical studies suggest that a 2:2 drug:Mg2+ complex forms a "heterodimer complex" with respect to DNA in which one drug molecule is intercalated into DNA and the second drug molecule is externally bound, held to the first molecule by two Mg2+ bridges, which themselves are chelated to phosphates on DNA. There is a cooperativity in binding of the quinobenzoxazines to DNA, and a 4:4 drug:Mg2+ complex is proposed in which the two externally bound molecules from two different 2:2 dimers interact via pi-pi interactions. The externally bound quinobenzoxazine molecules can be replaced by the quinolone antibacterial compound Norfloxacin to form mixed-structure dimers on DNA. Based upon the proposed model for the 2:2 quinobenzoxazine:Mg2+ complex on DNA, a parallel model for the antibacterial quinolone-Mg2(+)-DNA gyrase complex is proposed that relies upon the ATP-fueled unwinding of DNA by gyrase downstream of the cleavable complex site. These models, which have analogies to leucine zippers, represent a new paradigm for the structure of drug-DNA complexes. In addition, these models have important implications for the design of new gyrase and topoisomerase II inhibitors, in that optimization for structure-activity relationships should be carried out on two different quinolone molecules rather than a single molecule.

Animals↗

PubMed1995

The clonal composition of myelin basic protein-reactive encephalitogenic T cell populations is influenced both by the structure of relevant antigens and the nature of antigen-presenting cells.

Studies of experimental autoimmune encephalomyelitis (EAE) in rodents have revealed that encephalitogenic T cell lines reactive with myelin basic protein (BP) are frequently dominated by clones expressing a restricted T cell receptor repertoire. Using the rat EAE model, we have begun to examine the basis for clonal dominance within BP-reactive T cell lines. We find that variations introduced into the standard protocol of periodic antigen stimulation produce marked shifts in the representation of different clones within encephalitogenic T cell populations. For example, altering the source of antigen-presenting cells (APC), while holding antigen (BP) constant, and substituting BP from guinea pig (GPBP) for that of the rat antigen (RBP) with constant APC, both cause shifts in the composition of the dominant clones within BP-reactive T cell lines. Our results suggest that: (i) adherence to an invariant protocol of antigen challenge may lead to an underestimation of the diversity of BP-reactive encephalitogenic T cell populations; and (ii) the minor structural differences between GPBP and RBP not only cause the weak immunogenicity of RBP but also result in the alteration of different T cell subsets. These observations indicate that apparent restrictions upon the repertoire of autoimmune T cells should be interpreted with caution when such cells are elicited by immunization with foreign antigens.

Amino Acid Sequence↗

PubMed1995

Heterogeneity of rat encephalitogenic T cells elicited by variants of the myelin basic protein (68-86) peptide.

By immunizing Lewis rats with myelin basic protein (MBP) peptide variants derived from the major encephalitogenic epitope of guinea pig (MBP(68-88) and then isolating encephalitogenic T cells from these animals, we demonstrated that the variant peptides do not elicit the same encephalitogenic T cell subsets as those induced by the wild-type peptide or by intact MBP. Rather, the pathogenic T cells differed in clonal composition as reflected by their heterogeneous responses to a panel of variant peptides and by their T cell receptor usage. Thus, molecules mimicking the MBP(68-88) autoantigen can elicit pathogenic T cell subsets without necessarily cross-reacting with T cells specific for the original autoantigen. This suggests that a more clonally diverse group of pathogenic T cells might be involved in EAE than has been apparent from studies with intact MBP or its unaltered peptides.

Amino Acid Sequence↗

PubMed1995

Apolipophorin III is dramatically up-regulated during the programmed death of insect skeletal muscle and neurons.

The intersegmental muscles (ISMs) of the tobacco hawkmoth Manduca sexta, participate in the emergence behavior of the adult moth and then die during the subsequent 30 hours. In addition, several populations of interneurons and uniquely identified motor neurons also die after adult emergence. The trigger for all of these deaths is a decline in the circulating titer of the insect molting hormone 20-hydroxyecdysone. The ability of the muscles and neurons to die requires de novo gene expression. A differential hybridization screen of a "condemned" ISM cDNA library permitted the isolation of clones encoding four new up-regulated mRNAs. On sequencing, one of these recombinants was found to encode apolipophorin III (apoLp-III), a component of lipophorin, the major hemolymph lipoprotein of insects, previously shown to be synthesized in fat body. Although apoLp-III mRNA and protein were expressed at all stages of ISM development, levels of both molecules were dramatically elevated with the commitment of the cells to die. When ISM cell death was delayed by injection of 20-hydroxyecdysone, expression of apoLp-III at both the RNA and protein levels was markedly reduced at the normal time of cell death. Immunocytochemistry demonstrated that apoLp-III protein was abundantly expressed in the cytoplasm of dying muscles, interneurons, and identified motor neurons at the time of cell death. Apolipoproteins I and II, required components of lipophorin, were not expressed at detectable levels in the muscles or neurons. Furthermore, Western blots of native gels suggest that apoLp-III was not associated with any other proteins. These data suggest that apoLp-III has activities independent of lipid transport that may play a role in programmed cell death. ApoLp-III joins apolipoproteins E and J (clusterin, sulfated glycoprotein-2) as a group of proteins that function in both lipid transfer and cell death.

Animals↗

PubMed1995

The pattern of cytokine gene expression induced in rat T cells specific for myelin basic protein depends on the type and quality of antigenic stimulus.

Rat T cells reactive against myelin basic protein (MBP) are exclusively, CD4+ CD8- CD45RC-, inevitably produce abundant IFN-gamma, and appear to correspond to members of the Th1 CD4+ T cell subset characterized in mice. To ascertain the basis of the pathogenic activity of these cells, we studied their pattern of cytokine expression in response to activation by distinct TCR ligands. Using RT-PCR and Northern blot assays to quantify cytokine gene production and cytokine production from intact cells, we show that (i) rat MBP-reactive T cells express IL-2, IFN-gamma, and TNF-alpha as well as IL-5 and IL-10; (ii) cytokine production is not an all or nothing phenomenon, but rather varies according to the type and dose of TCR ligand, leading to variation in the pattern of cytokine production, or dissociation between cytokine production and cell proliferation; and (iii) nonencephalitogenic T cells do not differ appreciably from their encephalitogenic counterparts in ability to produce major cytokines.

Amino Acid Sequence↗

PubMed1995

TBP binding to the TATA box induces a specific downstream unwinding site that is targeted by pluramycin.

BACKGROUND: The TATA-binding protein (TBP) is one of the major components of the human TFIID multiprotein complex. It is important in directing the initiation of RNA transcription at a site immediately downstream of the TATA sequence (TATA box) found in many eukaryotic promoters. The crystal structure of TBP complexed with an oligonucleotide containing the TATA box revealed a protein with an approximate two-fold symmetry which apparently has symmetrical interactions with DNA. It is not known how an asymmetric effect involving downstream activation can be produced by an apparent symmetric complex. We set out to examine the state of DNA in the TBP-DNA complex using pluramycin, a small molecular weight probe of DNA accessibility. RESULTS: Binding of TBP to the TATA box facilitates intercalation of pluramycin at a defined site immediately downstream of the TATA sequence through an apparent transient unwinding of the DNA. Pluramycin adducts are detected by the production of DNA strand breakage products upon heating. Incubation of pluramycin with the TBP-DNA complex facilitates the trapping of the specific complex by intercalation. Gel mobility shift and circularization assays reveal that the binding of pluramycin on the 3'-side of the TATA box region considerably stabilizes the TBP-DNA complex. CONCLUSIONS: We propose that the TBP-DNA-pluramycin ternary complex is a 'specific' binding mode in which TBP and pluramycin make compensatory alterations in DNA, accounting for the improved stability of the ternary complex. We also propose a model of the ternary complex that explains the observed asymmetric effect of TBP binding to the TATA box.

Aminoglycosides↗

PubMed1995

Recurring oral giant cell lesion in a child with X-linked hypophosphatemic rickets: clinical manifestation of occult parathyroidism?

A 9-year-old boy with X-linked hypophosphatemic rickets had a recurring oral giant cell lesion. These lesions are relatively uncommon in children and represent a potentially aggressive disorder that is microscopically indistinguishable from the brown tumors of hyperparathyroidism. Subclinical hyperparathyroidism is not uncommon in X-linked hypophosphatemic rickets and may account for the giant cell lesion in this patient.

Biopsy↗

PubMed1995

Risk of acquiring AIDS from salivary exchange through cardiopulmonary resuscitation courses and mouth-to-mouth resuscitation.

In summary, the risk of transmission of HIV and other infectious diseases by saliva during CPR training practice is extremely low because of low infectious virus titers and properties of saliva that inhibit HIV. However, it is necessary to perform decontaminations of mannequins, by application of a suitable disinfectant and by a mechanical wipe-down with a sponge, to cleanse the external buccal area of the mannequin after contact with each CPR trainee. For health care and public safety professionals training and performance of MTM ventilation during CPR should be carried out with barrier devices such as the bag-valve-mask or face shield. Guidelines and standards of the AHA, American Red Cross, and the CDC for prevention of infection during CPR and emergency cardiac care are more fully available elsewhere. If the recommended procedures are followed, the risk of acquiring HIV from saliva during MTM should be extremely low.

Acquired Immunodeficiency Syndrome↗

PubMed1995

An MHC class II-expressing T cell clone presenting conventional antigen lacks the ability to present bacterial superantigen.

We have analyzed the response of rat T cells to myelin basic protein (MBP) and the bacterial superantigen, staphylococcal enterotoxin E (SEE). Rat T cells reactive with MBP can respond to SEE presented by spleen cells but not to SEE presented by LOA, a rat T cell clone that expresses both I-A and I-E MHC class II molecules, even though LOA is much more efficient than splenic APC in the presentation of MBP. The inability of LOA to present superantigen is not due to a structural difference in MHC II molecules between LOA and the splenic APC or to differential expression of major accessory/adhesion molecules, including CD2, CD5, CD4 and CD44, on LOA. The non-responsiveness of SEE/LOA-induced T cells differs from anergy, in that such cells do not lose their subsequent responsiveness to either MBP or SEE. Our results demonstrate that: (i) MHC class II molecules (I-A and I-E) alone are insufficient for the activation of T cells by bacterial superantigen, (ii) failure to respond to antigen presented upon inappropriate APC or in inadequate doses may not necessarily represent anergy, and (iii) the quality of the T cell response towards certain ligands can be strongly influenced by the nature of the APC.

Animals↗

PubMed1995

An autoregulated dual-function antitat gene for human immunodeficiency virus type 1 gene therapy.

One approach to gene therapy for AIDS is to block the replication of human immunodeficiency virus type 1 (HIV-1) by inhibiting that tat gene, whose product activates the expression of all HIV-1 genes. To accomplish this, we constructed an antitat gene expressing an RNA with dual (polymeric TAR and antisense-tat) function in an attempt to both sequester Tat protein and block its translation from mRNA. A minigene consisting of the antitat gene driven by the HIV-1 long terminal repeat was inserted into a double-copy retrovirus vector, such that antitat expression would be upregulated only in HIV-1-infected cells. After transduction of a T-lymphocytic cell line (Molt-3) the antitat gene inhibited HIV-1 replication. This inhibition was inversely correlated with the virus infections dose. Virus replication was also inhibited for 5 months in two different T-cell lines after they had been infected at a high multiplicity of infection, suggesting that the antitat gene may be effective over long periods. Importantly, antitat blocked the replication and the cytopathic effect of HIV-1 in human peripheral blood mononuclear cells and led to as much as 4,000-fold inhibition of the replication of an HIV-1 field isolate as well as HIV-1 prototypes maintained in culture. These results suggest that antitat gene therapy has potential use for blocking HIV-1 replication in infected individuals.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Cerebral microvascular endothelial cell Na-K-Cl cotransport: regulation by astrocyte-conditioned medium.

Brain microvascular endothelial cells play an important role in regulation of ion and fluid movement between the blood and the brain interstitium. Astrocytes have been shown to induce blood-brain barrier properties in the endothelial cells, including formation of tight junctions and increased expression and asymmetric distribution of enzymes and ion transport systems. Previous studies have demonstrated that endothelial cells of bovine aorta possess a highly active Na-K-Cl cotransport system that participates in intracellular volume regulation. The present study was conducted to evaluate Na-K-Cl cotransport activity of cerebral microvascular endothelial cells and to determine whether astrocyte-conditioned medium (CM) influences Na-K-Cl cotransport activity of these cells. We found the brain microvascular endothelial cells to exhibit a robust Na-K-Cl cotransport activity, comprising 50% of the total K influx. Activity of the cotransporter was stimulated by agents that elevate intracellular Ca and by hypertonicity and was inhibited by agents that elevate adenosine 3',5'-cyclic monophosphate, guanosine 3',5'-cyclic monophosphate, or activate protein kinase C. Exposure of the cells to primary astrocyte- or C6 glial cell-CM but not A7r5 or A10 vascular smooth muscle cell-CM also increased cotransport activity. However, this effect required > 1 h of exposure to CM, was additive with the effects of vasopressin, calcium ionophore, and hypertonicity, and was blocked by the protein synthesis inhibitor cycloheximide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Astroglial cell-induced expression of Na-K-Cl cotransporter in brain microvascular endothelial cells.

Endothelial cells of the blood-brain barrier (BBB) are characterized by extensive tight junctions and asymmetric distribution of specific enzymes and transport systems. Maintenance of the BBB endothelial phenotype depends on astrocyte-endothelial interactions. We showed previously that cultured cerebral microvascular endothelial cells (CMEC) exhibit robust Na-K-Cl cotransport activity. In the present study, we evaluated the expression of Na-K-Cl cotransport protein in CMEC by quantitative Western blot analysis and found that a protein of approximately 170 kDa was recognized by a monoclonal antibody against the cotransporter. Exposure of CMEC to astroglial cells or their conditioned media increased the expression of the CMEC cotransport protein by approximately 55%. Using a monoclonal antibody against the alpha-subunit of chicken Na-K-ATPase, we found that these treatments also increased expression of Na-K-ATPase protein by a similar amount. By comparing bumetanide-sensitive K influx and [3H]bumetanide binding apical vs. basolateral surfaces of CMEC, we found both cotransporter activity and [3H]bumetanide binding to be approximately 90% apical and 10% basolateral. Coculture of the CMEC with astroglial cells increased cotransport activity and [3H]bumetanide binding at both surfaces, with the asymmetric distribution maintained. These results indicate that the cotransporter is regulated by astroglial cells and that an apically distributed CMEC cotransporter may function in tandem with the basolateral Na-K-ATPase to mediate vectorial transport of Na and Cl across the BBB.

Animals↗

PubMed1995

Endothelial Na-K-Cl cotransport regulation by tonicity and hormones: phosphorylation of cotransport protein.

The Na-K-Cl cotransport system of vascular endothelial cells plays a central role in maintenance and regulation of intracellular volume. Activity of the cotransporter is modulated both by hormones and by extracellular tonicity. Vasopressin and other hormones that stimulate the endothelial cotransporter act via a Ca- and calmodulin-dependent pathway. Little is known, however, about the mechanisms that mediate cell shrinkage-induced stimulation of cotransport activity. In the present study, we evaluated the Ca dependence of cell shrinkage-stimulated Na-K-Cl cotransport activity and cell volume recovery of cultured bovine aortic endothelial cells and also the effects of protein kinase and phosphatase inhibitors on these processes. In addition, to investigate the possibility that hormones and/or hypertonicity regulate endothelial Na-K-Cl cotransport via direct phosphorylation of the cotransporter protein, we employed a monoclonal antibody to the human colonic T84 epithelial cell Na-K-Cl cotransport protein (T4 antibody) for Western blot analysis and immunoprecipitation of phosphoprotein. Our studies revealed that both cell shrinkage-stimulated net K uptake and recovery of intracellular volume were Ca dependent. We also found that hypertonicity-induced stimulation of cotransport activity was blocked by several inhibitors of Ca- and calmodulin-dependent protein kinases. Furthermore, inhibitors of myosin light chain kinase blocked cell shrinkage-stimulated cotransport and recovery of intracellular volume, while having no effect on vasopressin-stimulated cotransport. Western blot analysis of bovine aortic and cerebral microvascular endothelial cell membrane preparations revealed a 170-kDa protein recognized by the T4 antibody. In addition, we found that hypertonicity induced a marked increase in phosphorylation of the endothelial cotransport protein, as did vasopressin, bradykinin, okadaic acid, and calyculin A. Our findings indicate that modulation of endothelial cell Na-K-Cl cotransport activity by hypertonicity and by stimulatory hormones occurs via pathways involving Ca- and calmodulin-dependent protein kinases and direct phosphorylation of the cotransport protein.

Animals↗

PubMed1995

Exercise training augments flow-dependent dilation in rat skeletal muscle arterioles. Role of endothelial nitric oxide and prostaglandins.

We aimed to test the hypothesis that as a consequence of short-term daily exercise, flow (shear stress)-dependent dilation and its mediation by the endothelium are altered in skeletal muscle arterioles. After initial familiarization with the protocol, rats ran on a treadmill once a day (with gradually increasing intensity up to 40 minutes and 28 m/min) for approximately 3 weeks (EX group); a control group remained sedentary (SED group). The active (internal) diameters of isolated gracilis muscle arterioles of SED and EX rats at 80 mm Hg were significantly different (55.2 +/- 2.1 and 49.3 +/- 2.0 microns, P < .05), and their passive diameters (in Ca(2+)-free solution) were 105.3 +/- 3.1 and 111.2 +/- 2.4 microns (not significantly different), respectively. Increases in flow of the perfusion solution from 0 to 12 microL/min elicited a significantly greater increase in diameter of EX arterioles (by 83.5% at maximum flow). This enhanced sensitivity maintained a lower shear stress in EX arterioles (15 to 20 dyne/cm2) compared with SED arterioles (25 to 35 dyne/cm2). In both SED and EX arterioles, flow-dependent dilation was eliminated after removal of the endothelium. Either N omega-nitro-L-arginine, a nitric oxide synthase inhibitor, or indomethacin, an inhibitor of prostaglandin synthesis, shifted the flow-diameter and calculated wall shear stress-diameter curves significantly to the right. Each of the inhibitors reduced flow-dependent dilation to a similar degree (approximately 40% to 45%); their combined administration nearly completely eliminated the dilation of arterioles of both SED and EX rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗