Biomedical subjects

D Sun

Publications and source records attributed to D Sun.

At least 235 records · Page 13Linked to original sources

PubMed1997

Domains within the Vibrio cholerae toxin coregulated pilin subunit that mediate bacterial colonization.

Several experimental approaches have provided evidence suggesting that a domain within the C-terminal region of the TcpA pilin, delineated by the single disulfide loop, is directly responsible for the colonization function mediated by the toxin coregulated pilus (TCP) of Vibrio cholerae. This evidence includes the mapping of domains recognized by protective monoclonal antibodies to this region, the ability of peptides from within this region to elicit cholera protective antibody, the construction of tcpA missense mutations that abolish TCP function, and the requirement of a periplasmic disulfide isomerase to produce functional TCP.

Animals↗

PubMed1997

Expression of chemokine genes in rat glial cells: the effect of myelin basic protein-reactive encephalitogenic T cells.

Chemokine gene expression and chemokine activity appear to be major components of the immunopathological processes of inflammation and autoimmunity. To initiate an investigation of the role of chemokines in the pathogenesis of autoimmune inflammatory demyelination, we examined the expression of mRNA transcripts encoding four prominent chemokines, IP-10, MIP-1 alpha, MCP-1, and RANTES, in encephalitogenic rat MBP-reactive T cells, astrocytes, and microglia. Astrocytes and microglia, whether as lines or as freshly isolated cells, did not constitutively express IP-10 and MCP-1 mRNA but could be induced with LPS to also produce MIP-1 alpha and RANTES. MBP-reactive T cells were induced with MBP to produce abundant levels of MIP-1 alpha, MCP-1, and RANTES mRNA in different temporal profiles but did not express IP-10 mRNA. In an MHC-II restricted fashion, the antigen-activated MBP-reactive T cells also induced glial cells to express all four chemokines, with the chemokine gene expression greatest following T-cell interactions with MHC-compatible glia. Treatment of glial cells with TNF-alpha and IFN-gamma induced only IP-10, indicating that the expression of chemokine genes other than IP-10 requires a combination of different cytokines or direct cell-cell contact between T cells and glia. Quantitative assays revealed that activated astrocytes, the dominant glia of the CNS, express higher levels of chemokine transcripts than transcripts of the major proinflammatory cytokines TNF-alpha and IFN-gamma. These results underscore the prominent but complex expression of chemokines by cellular component of inflammatory demyelinating lesions.

Animals↗

PubMed1997

Analysis of genes for human snRNP Sm-D1 protein and identification of the promoter sequence which shows segmental homology to the promoters of Sm-E and U1 snRNA genes.

The Sm core proteins of U1, U2, U4/U6 and U5 snRNPs include B(B1), B'(B2), N(B3), D1, D2, D3, E, F and G polypeptides. We have isolated genomic clones encoding the Sm-D1 protein using the Sm-D1 cDNA as probe. Southern blotting and DNA sequencing analysis of these clones revealed the presence of an Sm-D1 multigene family in the human genome. Three gene members have been identified. Two of the genes are without introns and contain mutations compared to the cDNA sequence. They appear to be processed pseudogenes. The third gene, termed SNRPD1, shares 100% identity to the cDNA sequence including both 5'- and 3'-untranslated regions (UTR); it contains three introns. Analysis of the 5'-flanking region of the SNRPD1 gene revealed promoter activity, suggesting this is the functional gene that encodes the Sm-D1 protein. The promoter activity was localized in a 0.38 kb PstI fragment using CAT reporter gene fusion assays. Addition of an SV40 enhancer element did not enhance the transcription directed by that fragment. Sequence comparison of the 0.38 kb promoter sequence with the promoters of the Sm-E gene and U1 snRNA genes revealed several homologous motifs, suggesting that genes encoding the snRNP components may be coordinately regulated.

Amino Acid Sequence↗

PubMed1997

Screening of SLE sera using purified recombinant Sm-D1 protein from a baculovirus expression system.

The Sm-D1 polypeptide is a major target of autoantibodies diagnostic for systemic lupus erythematosus (SLE). The cDNA encoding the human antigen was expressed as a full-length, nonfusion protein using a eukaryotic baculovirus expression system. This recombinant version of Sm-D1 (rSm-D1) was purified to apparent homogeneity by a combination of differential extraction steps and FPLC chromatography. A direct antibody-binding ELISA was developed using the purified antigen. There was 96% correlation between the rSm-D1 and bona fide Sm-D1 from either HeLa cells or rabbit thymus when tested against Sm-positive patient sera by ELISA. The baculovirus-expressed Sm-D1 is reactive not only with patient anti-Sm sera, but also with anti-Sm monoclonal antibodies. Our results suggest that this rSm-D1 mimics the bona fide sources, providing a valuable addition to the roster of antigens available for SLE screening, epitope mapping and overall structure study.

Antibodies, Monoclonal↗

PubMed1997

Persistent myocardial ischemia increases GLUT1 glucose transporter expression in both ischemic and non-ischemic heart regions.

Persistently ischemic myocardium exhibits increased glucose uptake which may contribute to the preservation of myocardial function and viability. Little is known about the specific molecular events which are responsible for this increase in uptake. Therefore, we investigated whether myocardial ischemia induces the gene expression of the major cardiac facilitative glucose transporters, GLUT4 and GLUT1. We determined the expression of myocardial glucose transporter mRNAs and polypeptides after 6 h of regional ischemia in a dog model by semi-quantitative Northern blotting and immunoblotting. GLUT1 but not GLUT4 expression was significantly increased in both ischemic and non-ischemic regions from the experimental hearts when compared to surgical control and normal hearts. GLUT1 mRNA expression was increased 3.4-fold and GLUT1 polypeptide expression was increased 1.7-fold in ischemic hearts when compared to normal or surgical-control hearts. There were no significant regional differences in GLUT1 expression in either normal or ischemic hearts. However, there was a tendency for GLUT1 mRNA expression to be highest in the non-ischemic regions from the 6-h ischemia hearts. These findings suggest that myocardial ischemia induces a factor or factors which stimulate GLUT1 expression in non-ischemic as well as ischemic myocardial regions. Increased GLUT1 expression may play a role in augmenting glucose uptake during ischemia.

Animals↗

PubMed1997

Nonactivated astrocytes downregulate T cell receptor expression and reduce antigen-specific proliferation and cytokine production of myelin basic protein (MBP)-reactive T cells.

Astrocytes express variable levels of MHC class II antigens depending on their activation status or exposure to certain cytokines, notably IFN-gamma. When they are induced to express higher surface densities of MHC class II molecules, astrocytes are capable of stimulating syngeneic myelin basic protein (MBP)-reactive T cells to proliferate at a modest rate and to secrete proinflammatory cytokines, such as TNF-alpha, in response to antigen. In the present investigation evidence is presented that uninduced astrocytes, whether fresh or established as clones, on which surface MHC class II molecules are expressed at a very low density, promote an antigen-dependent reduction of TCR on the surface of syngeneic T cells. Accompanying this effect on the TCR is an induction of T cell hyporeactivity and little or no production of proinflammatory cytokines. These observations suggest that the ability of the astrocyte, through varying their surface MHC class II molecules, can control the effect of antigen-induced T cell responses. In their normal state of low MHC II expression astrocytes are expected to induce no or partial, rather than full, activation of autoreactive T cells that enter the CNS, resulting in T cell hyporeactivity. Since astrocytes usually diminish the production of proinflammatory cytokines by T cells that enter the CNS, the status and control of MHC class II expression on astrocytes should be important determinants of the suppression or enhancement of in situ immune responses in the CNS.

Animals↗

PubMed1997

Interstrain variability of autoimmune encephalomyelitis in rats: multiple encephalitogenic myelin basic protein epitopes for DA rats.

We investigated T cell epitopes of guinea pig myelin basic protein (MBP) that induce experimental autoimmune encephalomyelitis (EAE) in DA rats, using synthetic peptides that correspond to regions of the guinea pig MBP molecule that are homologous to rat MBP. Four peptides were encephalitogenic when tested in DA rats. MBP63-81, which partially overlaps the dominant encephalitogenic MBP epitope for Lewis (LEW) rats, caused severe EAE in the DA strain but did not elicit EAE in LEW rats. MBP66-81 and MBP63-76 were also encephalitogenic for DA but not LEW rats. MBP79-99 also induced EAE in DA rats, although MBP87-99, the minor encephalitogenic LEW epitope, was inactive. This indicates that part of the 79-86 sequence is necessary for encephalitogenic activity in the DA strain. MBP101-120, and MBP142-167 were also encephalitogenic for DA rats. T cells from DA rats immunized with intact MBP proliferated in response to the whole protein and to MBP79-99, but were not stimulated to a significant extent by the other encephalitogenic peptides, suggesting that these may represent cryptic or subdominant epitopes. However, MBP63-81-specific T cell lines could be isolated by repeated restimulation with peptide, indicating that the peptide-specific T cells were present in DA rats at low frequency.

Animals↗

PubMed1997

Preclinical and clinical strategies for development of telomerase and telomere inhibitors.

BACKGROUND: Telomerase is an important enzyme whose activity has been convincingly demonstrated in humans recently. It is required for maintenance of ends of chromosomes (telomeres) during cell division. Since its presence has been selectively demonstrated in dividing cells including tumor cells, it has generated considerable excitement as a potential anti-cancer strategy. DESIGN: In this article, we review the current relevant biology of the enzyme, the challenges encountered in the preclinical phase of target development and the current efforts that focus on telomeres and telomerase as therapeutic targets. We also speculate on the potential toxicities and mechanisms of resistance that may be encountered during use of such therapies.

Animals↗

PubMed1997

Promoter and intronic sequences of the human thiopurine S-methyltransferase (TPMT) gene isolated from a human PAC1 genomic library.

PURPOSE: To isolate and characterize the polymorphic human thiopurine S-methyltransferase (TPMT) gene. METHODS: The human TPMT gene was isolated by PCR screening of a phage artificial chromosome (PAC) library, using exon- and intron-specific primers, then mapped and sequenced. RESULTS: Two separate PAC1 clones were isolated that contained the same 25 kb gene with 9 exons encompassing the entire TPMT open reading frame. Structural characterization revealed distinct differences when compared to a TPMT gene previously isolated from a chromosome 6-specific human genomic library; the 5'-flanking region (putative promoter) contains 17 additional nucleotides located at position-77 upstream from the transcription start site, in addition to several nucleotide sequence differences, and intron 8 is only 1.6 kb, 5 kb shorter than previously reported. Southern and PCR analyses of genomic DNA from 18 unrelated individuals revealed only the TPMT gene structure corresponding to the PAC clones we isolated. Analysis of the TPMT promoter activity using the 5'-terminal region confirmed transcriptional activity in human HepG2 and CCRF-CEM cells. The 5'-flank is 71% GC rich and does not contain consensus sequences for TATA box or CCAAT elements. FISH analysis demonstrated the presence of the TPMT-homologous sequence on the short arm of chromosome 6 (sublocalized to 6p22). CONCLUSIONS: These findings establish the genomic structure of the human TPMT gene, revealing differences in the promoter and intronic sequences compared to that previously reported and providing a basis for future studies to further elucidate its biological function and regulation.

Bacteriophages↗

PubMed1997

Effects of sodium nitroprusside in the rat cortical collecting duct are independent of the NO pathway.

Recently we described K+ channels in the basolateral membrane of principal cells of rat cortical collecting duct (CCD) which are regulated by a cGMP-dependent protein kinase (Pflugers Arch 429:338-344, 1995). We examined the effects of the NO-liberator sodium nitroprusside (SNP) on single channel activity and membrane voltage (Vm) in principal cells of rat CCD, and on transepithelial voltage, lumen-to-bath Na+ fluxes, and osmotic water permeability in isolated perfused rat CCD tubules. While in patch clamp experiments SNP (10 microM) hyperpolarized principal cells from -54 +/- 10 mV to -71 +/- 5 mV (N = 5) and increased the activity of the described K+ channels from 0.05 +/- 0.03 to 0.45 +/- 0.14 (N = 5) in cell-attached and from 0.04 +/- 0.02 to 0.25 +/- 0.05 (N = 4) in excised patch clamp experiments, it had no effect on basal or AVP-dependent transepithelial voltage, Na+ fluxes, or the osmotic water permeability. In addition, neither 50 microM SIN-1, another liberator of NO, nor 1 mM L-NAME, an inhibitor of the NO-synthase, changed Vm significantly. Furthermore, in cGMP-assays SNP failed to increase intracellular cGMP in CCD segments. Thus, we conclude that in the rat CCD transport is not regulated via the NO-pathway and that SNP acts as an cGMP independent activator of K+ channels in the basolateral membrane of these cells.

Animals↗

PubMed1997

Assembly properties of amino- and carboxyl-terminally truncated neurofilament NF-H proteins with NF-L and NF-M in the presence and absence of vimentin.

To understand the assembly characteristics of the high-molecular-weight neurofilament protein (NF-H), carboxyl- and amino-terminally deleted NF-H proteins were examined by transiently cotransfecting mutant NF-H constructs with the other neurofilament triplet proteins, low- and middle-molecular-weight neurofilament protein (NF-L and NF-M, respectively), in the presence or absence of cytoplasmic vimentin. The results confirm that NF-H can coassemble with vimentin and NF-L but not with NF-M into filamentous networks. Deletions from the amino-terminus show that the N-terminal head is necessary for the coassembly of NF-H with vimentin, NF-L, or NF-M/vimentin. However, headless NF-H or NF-H from which the head and a part of the rod is removed can still incorporate into an NF-L/vimentin network. Deletion of the carboxyl-terminal tail of NF-H shows that this region is not essential for coassembly with vimentin but is important for coassembly with NF-L into an extensive filamentous network. Carboxyl-terminal deletion into the alpha-helical rod results in a dominant-negative mutant, which disrupts all the intermediate filament networks. These results indicate that NF-L is the preferred partner of NF-H over vimentin and NF-M, the head region of NF-H is important for the formation of NF-L/NF-H filaments, and the tail region of NF-H is important to form an extensive network of NF-L/NF-H filaments.

Base Sequence↗

PubMed1997

Development and application of ultrasonic surgical instruments.

In this paper, a new approach for designing ultrasonic surgical instruments (USI) is presented. These medical instruments convert an ultrasonic signal into a mechanical vibration by utilizing a magnetostrictive method and have been found to be very useful for various medical procedures. The implemented system consists of an ultrasonic generator, a transducer, and waveguide instruments. The generator produces a high-current ultrasonic signal. The transducer converts this signal into a mechanical vibration. By use of the waveguide instrument, the vibration can be propagated and amplified. This new type of USI possesses a comprehensive ability to stop bleeding, cut bone tissues, regulate frequency automatically, control temperature, etc. The results from animal experiments and from human clinical operations show that the developed USI has the advantages in various aspects over the conventional equipment.

Abdominal Muscles↗

PubMed1997

Role of the extracellular domain of human herpesvirus 7 glycoprotein B in virus binding to cell surface heparan sulfate proteoglycans.

In an attempt to identify the human herpesvirus 7 (HHV-7) envelope protein(s) involved in cell surface binding, the extracellular domain of the HHV-7 glycoprotein B (gB) homolog protein was cloned and expressed as a fusion product with the Fc domain of human immunoglobulin G heavy chain gamma1 (gB-Fc) in an eukaryotic cell system. Indirect immunofluorescence followed by flow cytometric analysis revealed specific binding of gB-Fc to the membrane of SupT1 cells but not to other CD4+ T-lymphoblastoid cell lines, such as Jurkat or PM1, clearly indicating that gB-Fc did not bind to the CD4 molecule. This was also suggested by the ability of gB-Fc to bind to CD4-negative fibroblastoid Chinese hamster ovary (CHO) cells. The binding was abrogated by enzymatic removal of cell surface heparan sulfate proteoglycans by heparinase and heparitinase but not by treatment with condroitinase ABC. In addition, binding of the gB-Fc fusion protein to CHO cells was severely impaired in the presence of soluble heparin, as well as when heparan sulfate-deficient mutant CHO cells were used. Consistent with these findings, soluble heparin was found to block HHV-7 infection and syncytium formation in the SupT1 cell line. Although the CD4 antigen is a critical component of the receptor for the T-lymphotropic HHV-7, these findings suggest that heparin-like molecules also play an important role in HHV-7-cell surface interactions required for infection and that gB represents one of the HHV-7 envelope proteins involved in the adsorption of virus-to-cell surface proteoglycans.

Animals↗

PubMed1997

IL-6 secreted by astroglial cells regulates Na-K-Cl cotransport in brain microvessel endothelial cells.

We showed previously that cerebral microvessel endothelial cells (CMEC) exhibit a prominent Na-K-Cl cotransporter that functions to regulate intracellular volume and may also mediate vectorial ion transport across the blood-brain barrier (BBB). Astrocytes and their conditioned media induce BBB properties of the endothelium. Our previous studies demonstrated that exposure of CMEC to astroglial cells markedly increases cotransport activity, upregulates cotransporter protein expression, and also increases cotransporter protein phosphorylation. In the present study, we evaluated the possibility that astroglial effects on the Na-K-Cl cotransporter are mediated by astroglial cell-secreted interleukin-6 (IL-6). Cotransporter activity was assessed as bumetanide-sensitive K influx, and protein expression was evaluated by Western blot analysis. Exposing CMEC to IL-6 for 48 h caused a dose-dependent stimulation of Na-K-Cl cotransport activity. Both C6 glial cell-conditioned medium (C6CM)-induced and IL-6-induced increases in cotransport activity were neutralized by anti-IL-6 antibodies. A 48-h exposure of cells to IL-6 or C6CM also resulted in increased cotransporter protein expression. Furthermore, using an enzyme-linked immunosorbent assay for IL-6, we found significant amounts of IL-6 in C6CM. These data suggest that astroglia-secreted IL-6 may mediate the observed astroglial cell effects on CMEC Na-K-Cl cotransport and further support the hypothesis that astrocytes participate in maintenance of cerebral ionic homeostasis by regulating Na-K-Cl cotransporter function at the BBB.

Animals↗

PubMed1997

Molecular characterization of the Na-K-Cl cotransporter of bovine aortic endothelial cells.

The Na-K-Cl cotransporter is an important regulator of endothelial cell volume and may also contribute to flux of Na and Cl across the endothelium of the blood-brain barrier. To date, two Na-K-Cl cotransport isoforms have been identified, the cotransporter in secretory epithelia, NKCC1, and that in absorptive renal epithelia, NKCC2. Our previous studies showed that a monoclonal antibody to the cotransporter of human colonic T84 epithelial cells, an NKCC1 isoform, recognizes a 170-kDa glycoprotein from endothelial cells. The molecular identity of the Na-K-Cl cotransporter present in endothelial cells, however, has been unknown. In addition, although evidence has been provided that phosphorylation of the endothelial cotransporter plays a role in regulating its activity, little is known about potential sites for protein kinase interaction with the cotransporter. The present study was conducted to determine the molecular structure of the endothelial Na-K-Cl cotransporter. Using a 1.0-kilobase (kb) cDNA fragment from a conserved region of the T84 cell cotransporter, we screened a bovine aortic endothelial cell cDNA library and subsequently identified and sequenced two overlapping clones that together spanned the entire coding region. The endothelial cotransporter is a 1,201-amino acid protein with 12 putative transmembrane segments and large amino and carboxy termini, each containing several consensus sites for phosphorylation by protein kinases. Comparison of the endothelial cotransporter amino acid sequence with known NKCC1 and NKCC2 sequences revealed a 96% identity with NKCC1. Northern blot analysis using a cDNA probe from the endothelial cotransporter revealed high expression of approximately 7.5-kb transcripts in a number of bovine tissues. Finally, a prominent expression of Na-K-Cl cotransporter was found by Western blot analysis in both cultured and freshly isolated endothelial cells of bovine aorta and cerebral microvessels.

Amino Acid Sequence↗

PubMed1997

Gender difference in myogenic tone of rat arterioles is due to estrogen-induced, enhanced release of NO.

The characteristics of arteriolar myogenic responses of female rats have not been investigated. Thus experiments were conducted on isolated gracilis muscle arterioles (approximately 55 microm diameter) of four groups of 12-wk-old rats: male rats, female rats, ovariectomized female rats with no estrogen replacement (OV), and ovariectomized female rats with estrogen replacement (OV + E2, 50 microg/kg s.c. injection of 17beta-estradiol benzoate every 48 h). Diameter changes in response to increases in perfusion pressure from 20 to 140 mmHg and to various concentrations of substance P (SP, 10(-9)-5 x 10(-8) M) and sodium nitroprusside (SNP, 10(-8)-10(-6) M) were measured before and after administration of N(omega)-nitro-L-arginine (L-NNA, 10(-4) M), an inhibitor of NO synthase. Arteriolar diameters of male and OV female rats were significantly less at 60-140 mmHg pressure than those of normal female and OV + E2 female rats (at 80 mmHg, 45.4 +/- 1.8 and 43.1 +/- 2.2 vs. 58.4 +/- 1.6 and 57.3 +/- 1.3%). L-NNA elicited a significantly greater downward shift of pressure-diameter curves in arterioles of normal female and OV + E2 female rats than in arterioles of male and OV female rats (28.6 +/- 4.6 and 30.6 +/- 4.7 vs. 13.2 +/- 0.9 and 10.4 +/- 2.6%). Dilations of arterioles from normal female and OV +/- E2 female rats to SP were significantly greater (by 50-60%) than those from male and OV female rats (20.8 +/- 1.8 and 22.3 +/- 1.9 vs. 13.8 +/- 1.4 and 13.8 +/- 0.6% at 10(-8) M). L-NNA did not affect dilations to SNP but significantly reduced the dilation of arterioles in all groups to SP, more so in arterioles of male and OV female rats than in arterioles of the other two groups. We conclude that pressure-induced myogenic constriction of arterioles of female rats is less pronounced than that of male rats; this is, most likely, due to the enhanced release and/or activity of NO related to the presence of estrogen.

Animals↗

PubMed1997

Identification of envelope glycoproteins H and B homologues of human herpesvirus 7.

The genes encoding the envelope glycoprotein H (gH) and gB homologues were identified by sequencing genomic clones of human herpesvirus-7 (HHV-7), strain JI. A gB cDNA clone from HHV-7 strain AL was also identified. The deduced primary translation products of the gH and gB genes are a protein of 690 amino acids, with a predicted mass of 80.4 kD, and a protein of 822 amino acids, with a predicted mass of 93.3 kD, respectively. Both the predicted proteins have the characteristics of transmembrane glycoproteins, containing signal and transmembrane sequence motifs and characterized by the presence of 10 (gH) and 11 (gB) potential motifs for N-glycosylation. Comparison of amino acid sequence of HHV-7 gH and gB with the homologous sequences of the other human herpesviruses reveals closest homology with HHV-6 (38.8% identity for gH, 56.2% identity for the gB). In addition, significant sequence similarity was also observed between the gH and gB of HHV-7 and the homologs encoded by human cytomegalovirus (21.6% identity for gH, 37.6% identity for gB). No significant differences existed between the gB sequence of the two different HHV-7 strains analyzed. The products of the HHV-7 gH and gB expressed transiently in eukaryotic cells were specifically recognized by an HHV-7-reactive human serum in immunofluorescence assays.

Adult↗

PubMed1997

Estrogen maintains nitric oxide synthesis in arterioles of female hypertensive rats.

We hypothesized that in female spontaneously hypertensive rats (SHR), estrogen moderates the dysfunction of arterioles by preserving nitric oxide synthesis. To this end, we conducted experiments on isolated gracilis muscle arterioles (approximately 55 microns in diameter) of 12-week-old (SHR divided into four groups: females (fSHR), ovariectomized females (fSHR-OV), ovariectomized females with estrogen replacement (fSHR-OV+ES, 50 micrograms/kg SC 17 beta-estradiol benzoate every 48 hours), and males (mSHR). Arteriolar diameter in the presence of perfusion pressures of 60, 80, 100, and 120 mm Hg were obtained, and diameter changes were measured (at 80 mm Hg) in response to various concentrations of substance P (10(-9) to 5 x 10(-8) mol/L), sodium nitroprusside (10(-8) to 10(-6) mol/L), and A23187 (5 x 10(-8) to 10(-6) mol/L). The pressure-induced diameter of mSHR and fSHR-OV arterioles was significantly less (by approximately 10%) than that of fSHR and fSHR-OV+ES arterioles. N omega-nitro-L-arginine (10(-4) mol/L), a nitric oxide synthase inhibitor, elicited a significant decrease in basal arteriolar diameter of fSHR (by approximately 19%) and fSHR-OV+ES (by approximately 17%), thereby eliminating the differences in tone among the various groups. Dilations of fSHR and fSHR-OV+ES arterioles to substance P were significantly greater (by 140% at a concentration of 5 x 10(-8) mol/L) than those of mSHR and fSHR-OV arterioles, whereas dilations to sodium nitroprusside were not different among the groups. A23187 (a nitric oxide releaser) elicited dilations in arterioles of fSHR (5.9 +/- 1.5%, 13.0 +/- 1.8%, and 19.2 +/- 2.1%) and fSHR-OV+ES (4.3 +/- 1.0%, 10.3 +/- 2.4%, and 15.0 +/- 4.0%) but constrictions in those of mSHR (-7.5 +/- 1.6%, -25.3 +/- 39%, and -36.9 +/- 4.1%) and fSHR-OV (-2.6 +/- 1.7%, 7.4 +/- 3.3%, and -11.5 +/- 6.1%). We conclude that estrogen in fSHR is responsible for the preservation of nitric oxide synthesis in skeletal muscle arterioles, resulting in a greater modulation of pressure-induced myogenic tone than in mSHR and maintenance of nitric oxide-mediated dilations.

Animals↗