Search PubMed⌕ Search

Biomedical subjects

D Boyd

Publications and source records attributed to D Boyd.

At least 37 records · Page 2Linked to original sources
PubMed2000

Candida albicans: adherence, signaling and virulence.

The focus of this symposium was to present new information on the morphogenesis of Candida albicans, particularly how it relates to signal transduction pathways and other genes involved in the regulation of morphogenesis. In addition, we discuss the role of adherence and colonization of the oral cavity by the organism and discuss the role of mannan as an adhesin that recognizes the human red blood cell. C. albicans utilizes at least two signal pathways to regulate its conversion from a yeast form to filamentous growth (hyphae). One of these two pathways is similar to the Saccharomyces cerevisiae pseudohyphal/mating pathway, which utilizes the regulatory protein, Cphlp. The other pathway is not totally defined but requires a second regulatory protein, referred to as Efg1p. Other signal pathways may exist, which include a two-component histidine kinase and response regulator proteins. The latter pathway(s) may include proteins such as Chk1p, Ssk1p, Shi1p and Cos1p/Nik1p. Mutations in strains, which specifically target these proteins, result in morphogenesis defects and avirulence or attenuation of strains. A growth regulatory gene has also been recently defined whose expression is associated with growth cessation and which appears to be a necessary prerequisite in conversion of the organism to a filamentous growth form. Starvation of yeast cells induces exponentially grown cells (and usually non-germinative) to germinate. This phenomenon is also observed in cells that are transiently treated with metabolic inhibitors. During each of these treatments (starvation, metabolic inhibition), expression of a growth regulatory gene (CGRI) increases. Adherence of C. albicans to host cells and tissues is complex; several proteins, which appear to have host recognition functions, have been defined. In the oral cavity, C. albicans selectively adheres to salivary proteins, which are absorbed to many oral surfaces. This mechanism enables the cells to colonize surfaces of the oral cavity. An understanding of these interactions may lead to strategies to prevent oral disease. Mannan from C. albicans may provide a host recognition function for C. albicans. Recent experiments indicate that mannan binds to human red blood cells and causes hemolysis. Binding of mannan to the band 3 protein of human red blood cells has been established. This activity may be associated with the ability of the organism to utilize hemoglobin (and iron).

Candida albicans↗
PubMed1999

Regulation of BAD phosphorylation at serine 112 by the Ras-mitogen-activated protein kinase pathway.

The function of the pro-apoptotic molecule BAD is regulated by phosphorylation of two sites, serine-112 (Ser-112) and serine-136 (Ser-136). Phosphorylation at either site results in loss of the ability of BAD to heterodimerize with the survival proteins BCL-XL or BCL-2. Phosphorylated BAD binds to 14-3-3 and is sequestered in the cytoplasm. It has been shown that phosphorylation of BAD at Ser-136 is mediated by the serine/threonine protein kinase Akt-1/PKB which is downstream of phosphatidylinositol 3-kinase (PI3K). The signaling process leading to phophorylation of BAD at Ser-112 has not been identified. In this study, we show that phosphorylation of the two serine residues of BAD is differentially regulated. While Ser-136 phosphorylation is concordant with activation of Akt, Ser-112 phosphorylation does not correlate with Akt activation. Instead, we demonstrate that activated Ras and Raf, which are upstream of mitogen-activated protein kinases (MAPK), stimulate selective phosphorylation of BAD at Ser-112. Furthermore, phosphorylation of Ser-112, but not Ser-136 requires activation of the MAPK pathway as the MEK inhibitor, PD 98059, blocks EGF-, as well as activated Ras- or Raf-mediated phosphorylation of BAD at Ser-112. Therefore, the PI3K-Akt and Ras-MAPK pathways converge at BAD by mediating phosphorylation of distinct serine residues.

3T3 Cells↗
PubMed1999

Measurement of matrix metalloproteinases and tissue inhibitors of metalloproteinases in blood and tissues. Clinical and experimental applications.

The balance between production and activation of MMPs and their inhibition by TIMPs is a crucial aspect of cancer invasion and metastasis. On the basis of the concept that MMPs synthesized in tissues seep into the bloodstream, we have examined MMP levels in the plasma of patients with cancer. In colorectal, breast, prostate, and bladder cancer, most patients with aggressive disease have increased plasma levels of gelatinase B. In patients with advanced colorectal cancer, high levels of either gelatinase B or TIMP complex were associated with shortened survival. We propose that these assays may be clinically useful in characterizing metastatic potential in selected kinds of cancer. In rheumatoid arthritis and systemic lupus erythematosus (SLE), serum and plasma levels of stromelysin-1 were approximately 3-5-fold increased. Fluctuating serum stromelysin-1 levels in SLE did not correspond with change in disease activity. In SLE, stromelysin-1 may be a component of the chronic tissue repair process rather than being responsible for inciting tissue damage. On the basis of these observations, we conclude that measurement of plasma/serum MMP and TIMP levels may provide important data for selecting and following patients considered for treatment with drugs that interfere with MMP activity.

Antigens, CD↗
PubMed1999

Characterization and proposed nomenclature of epidemic strains of methicillin-resistant Staphylococcus aureus in Canada.

We hope that standardized nomenclature for identifying epidemic MRSA strains prevalent in Canadian hospitals will be helpful to physicians and infection control practitioners attempting to understand and control the spread of the organism in health-care facilities. It is anticipated that as MRSA continues to evolve in Canadian health-care facilities other strains may be recognized as "epidemic"; as these strains become better characterized they may be added to those designated above. Laboratory physicians and infection control personnel are invited to submit strains that may warrant characterization and designation as a Canadian epidemic strain to the Laboratory Centre for Disease Control, Health Canada, Winnipeg, Manitoba.

Canada↗
PubMed1999

Transactivation of the urokinase-type plasminogen activator receptor gene through a novel promoter motif bound with an activator protein-2alpha-related factor.

The urokinase receptor overexpressed in invasive cancers promotes laminin degradation. The current study was undertaken to identify cis elements and trans-acting factors activating urokinase receptor expression through a footprinted (-148/-124) region of the promoter containing putative activator protein-2- and Sp1-binding motifs. Mobility shifting experiments using nuclear extract from a high urokinase receptor-expressing cell line (RKO) indicated that Sp1, Sp3, and a factor similar to, but distinct from, activator protein-2alpha bound to this region. Mutations preventing the binding of the activator protein 2alpha-related factor diminished urokinase receptor promoter activity. In RKO cells, the expression of a negative regulator of activator protein-2 function diminished urokinase receptor promoter activity, protein, and laminin degradation. Conversely, urokinase receptor promoter activity in low urokinase receptor-expressing GEO cells was increased by activator protein-2alphaA expression. Although using GEO nuclear extract, little activator protein-2alpha-related factor bound to the footprinted region, phorbol 12-myristate 13-acetate treatment, which induces urokinase receptor expression, increased complex formation. Mutations preventing the activator protein-2alpha-related factor and Sp1/Sp3 binding reduced urokinase receptor promoter stimulation by this agent. Thus, the constitutive and phorbol 12-myristate 13-acetate-inducible expression of the urokinase receptor is mediated partly through trans-activation of the promoter via a sequence (-152/-135) bound with an activator protein-2alpha-related factor.

Base Sequence↗
PubMed1999

A mutational study of the ArcA-P binding sequences in the aldA promoter of Escherichia coli.

The aldA gene (encoding aldehyde dehydrogenase) of Escherichia coli is anaerobically repressed by ArcA-P, the phosphorylated response regulator of the ArcB/A two-component signal transduction system. The promoter region of aldA contains two 10-bp sequences (5'-TGTTAATTAA-3') that perfectly match the proposed ArcA-P binding consensus (5'-[A/T]GTTAATTA[A/T]-3'). One consensus sequence is on the coding strand (-13 to -4 from the transcriptional start point), whereas the other is on the template strand (position -2 to -11). In this study we used the aldA promoter to test the validity of the proposed consensus sequence. DNase I protection experiments confirmed the 10-bp sequence to be a strong ArcA-P binding site. Alteration of the wild-type sequence from 5'-TGTTAATTAAC-3' to 5'-TCTTAATTAAG-3' or 5'-TATTAATTAAT-3' by site-directed mutagenesis markedly decreased the in vitro affinity of the promoter region for ArcA-P, and abolished the anaerobic repression of mutant att lambda::phi (aldA'-lacZ) transcriptional reporter constructs. Both the in vitro and in vivo results therefore support the proposed consensus sequence.

Aldehyde Dehydrogenase↗
PubMed1999

PD 098059, an inhibitor of ERK1 activation, attenuates the in vivo invasiveness of head and neck squamous cell carcinoma.

Increased mortality of patients with oral cancer largely reflects the local and regional spread of the disease. The invasiveness of these tumours requires hydrolases which are regulated through AP-1-dependent transcriptional mechanisms. Since the amount/activity of transcription factors bound to the AP-1 motif are regulated partly through the extracellular signal-regulated kinases (ERK1/ERK2), we determined the effect of PD 098059, an inhibitor of ERK1/ERK2 activation, on the in vivo invasiveness of a human squamous cell carcinoma cell line (UM-SCC-1) derived from the oral cavity. We utilized the floor of mouth musculature consisting of the mylohyoid, geniohyoid and genioglossus muscle (which are sequentially arranged), as a natural barrier to assess tumour spread in vivo in the nude mouse. Mice were inoculated with tumour cells superficial to the mylohyoid muscle. After 18 days, tumours were injected with either empty liposomes (control) or liposomes containing 5 microM PD 098059 and, after an additional 22 days, the jaws of mice examined histologically. Highly infiltrative tumours, which had penetrated the genioglossus muscle, were evident in 10/12 control mice. In contrast, in 9/12 mice in which the tumours were injected with PD 098059, tumours did not extend beyond the mylohyoid or geniohyoid muscles. Tumours penetrated bone nutrient canals in 7/12 control mice but in only 3/12 PD 098059-treated mice. Neurotropism, characteristic of aggressive oral squamous cell carcinoma, was evident in 6/12 control mice but was completely abolished (0/12 mice) in the PD 098059-treated mice. Using a staging system based on the muscle layer involved, neurotropism, as well as bone involvement, we found the inhibition of invasion to be statistically significant (P < 0.01). The reduced invasiveness of the PD 098059-liposome-treated oral cancers was associated with diminished 92-kDa type IV collagenase and ERK1/ERK2 activities but was not a consequence of a slower tumour growth rate. This is the first study to demonstrate reduced in vivo invasiveness of a malignancy brought about by an inhibitor of ERK1/ERK2 activation. These results raise the exciting possibility that second generation PD 098059 congeners may reduce the spread of the disease in patients afflicted with oral cancers.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1999

Targeted disruption of the K-ras oncogene in an invasive colon cancer cell line down-regulates urokinase receptor expression and plasminogen-dependent proteolysis.

The urokinase receptor, overexpressed in invasive colon cancer, promotes tumour cell invasion. Since K-Ras is activated in many colon cancers, we determined if urokinase receptor overexpression is a consequence of this activated oncogene. Accordingly, urokinase receptor expression was compared in HCT 116 colon cancer cells containing either a mutation-activated K-Ras or disrupted for this oncogene (by homologous recombination). HCT 116 cells containing the disrupted K-Ras oncogene expressed between 50 and 85% less urokinase receptor protein compared with the parental HCT 116 cells. Reduced urokinase receptor expression in cells containing the disrupted mutated K-Ras was not due to a physical impairment of the urokinase receptor gene since phorbol ester treatment was inductive for its expression. Constitutive urokinase receptor expression in HCT 116 cells required an intact AP-1 motif in the promoter (at -184) and electrophoretic mobility shifting assays indicated less c-Jun, JunD, c-Fos and Fra-1 bound to this motif in the K-Ras-disrupted cells. Since the urokinase receptor accelerates proteolysis, laminin degradation was compared in cells containing the mutation-activated and disrupted K-Ras oncogene. The latter cells displaying fewer urokinase receptors, degraded 80% less laminin. This is the first study to demonstrate a role for K-Ras as a regulator of the constitutive expression of the urokinase receptor.

Cell Nucleus↗
PubMed1999

A region between -141 and -61 bp containing a proximal AP-1 is essential for constitutive expression of urokinase-type plasminogen activator receptor.

An 8.5-kb 5'-flanking region of the human urokinase-type plasminogen activator receptor (uPAR) gene was cloned and the detailed uPAR promoter region defined in an 188-bp fragment between bases -141 and +47 relative to the transcription-start site. 5'-Deletion to -100 and -60 in the region abolished its promoter activity, indicating that an 81-bp segment between -141 and -61, which contains a proximal AP-1 site at position -70, is required for uPAR promoter activity. Nuclear extracts from HCT116 cells contain proteins that specifically bind to the AP-1 site. Mutation of the AP-1 motif reduced uPAR promoter activity in comparison with the wild-types. Induction of uPAR expression by phorbol ester requires this AP-1 motif in colon cancer cells. Cotransfection with the c-jun and c-fos expression vectors stimulated the uPAR promoter activity four- to fivefold. These results demonstrate that the proximal AP-1 motif is responsible for approximately 50% of the basal expression of the uPAR gene.

Base Sequence↗
PubMed1999

Localization of FtsI (PBP3) to the septal ring requires its membrane anchor, the Z ring, FtsA, FtsQ, and FtsL.

Assembly of the division septum in bacteria is mediated by several proteins that localize to the division site. One of these, FtsI (also called penicillin-binding protein 3) of Escherichia coli, consists of a short cytoplasmic domain, a single membrane-spanning segment, and a large periplasmic domain that encodes a transpeptidase activity involved in synthesis of septal peptidoglycan. We have constructed a merodiploid strain with a wild-type copy of ftsI at the normal chromosomal locus and a genetic fusion of ftsI to the green fluorescent protein (gfp) at the lambda attachment site. gfp-ftsI was expressed at physiologically appropriate levels under control of a regulatable promoter. Consistent with previous results based on immunofluorescence microscopy GFP-FtsI localized to the division site during the later stages of cell growth and throughout septation. Localization of GFP-FtsI to the cell pole(s) was not observed unless the protein was overproduced about 10-fold. Membrane anchor alterations shown previously to impair division but not membrane insertion or transpeptidase activity were found to interfere with localization of GFP-FtsI to the division site. In contrast, GFP-FtsI localized well in the presence of beta-lactam antibiotics that inhibit the transpeptidase activity of FtsI. Septal localization depended upon every other division protein tested (FtsZ, FtsA, FtsQ, and FtsL). We conclude that FtsI is a late recruit to the division site, and that its localization depends on an intact membrane anchor.

Bacterial Proteins↗
PubMed1999

Organochlorine contaminant levels in Eskimo harvested bowhead whales of arctic Alaska.

Organochlorine (OC) levels in liver and blubber of 20 bowhead whales (Balaena mysticetus) collected during the Eskimo subsistence harvest at Barrow (Alaska, USA) in 1992 and 1993 are presented. Liver sum DDT (lipid weight) was significantly greater in male whales than in females. Most of the organochlorines measured were at higher levels in longer (older) than in shorter (younger) males. For female bowhead whales, hexachlorobenzene and lipid levels decreased and other OC levels did not change significantly with increasing length. Most organochlorine contaminants have low concentrations in tissues of the bowhead whale compared to concentrations in tissues of other cetaceans, especially Odontocetes. Based on allowable daily intakes (ADI) levels established by the Canadian Northern Contaminants Program (Ottawa, Ontario, Canada) "safe" levels of blubber to consume were calculated. Chlordane levels in bowhead whale blubber results in the most restrictive consumption amount (50 g blubber/day). We expect no adverse effects related to these organochlorine contaminants to occur in bowhead whales or in consumers of their tissues. However, investigation of low level chronic exposure effects and a more rigorous assessment of histopathology, biomarkers, and immune status in the bowhead whale would be required to conclude "no effect" with more certainty.

Adipose Tissue↗
PubMed1998

Stimulation of urokinase-type plasminogen activator receptor expression by PMA requires JNK1-dependent and -independent signaling modules.

The urokinase-type plasminogen activator receptor (u-PAR) has been implicated in tumor progression, and previous studies have shown that the expression of this gene is strongly up-regulated by PMA. Although the signaling mechanism by which PMA modulates u-PAR expression is not known, the effect of this phorbol ester on the expression of other genes has been ascribed to activation of the c-Raf-1-ERK signaling pathway. However, in the current study we examined an alternate possibility that the inductive effect of PMA on u-PAR expression also required a JNK1-dependent signaling cascade usually associated with stress-inducing stimuli. PMA treatment of the u-PAR-deficient OVCAR-3 ovarian cancer cells, which contain low JNK activities, resulted in a rapid (5 min) increase in JNK activity. Maximal JNK activity (12-fold induction) occurred after 30 min; this preceding the earliest detected rise in u-PAR protein (2 h). Dose-response studies with PMA also indicated that the increased JNK activity was tightly correlated with elevated u-PAR protein levels. The stimulation of u-PAR promoter activity by PMA required an intact upstream AP-1 motif (-184) and in PMA-treated cells this motif was bound with c-Jun as indicated from mobility shift assays. PMA up-regulated the c-Jun trans acting activity as indicated by the higher activity of a GAL4-regulated luciferase reporter in phorbol-ester-treated cells co-transfected with an expression vector encoding the c-Jun transactivation domain fused to the GAL4 DNA-binding domain. The ability of PMA to stimulate u-PAR promoter activity was effectively titrated out by the co-expression of either a kinase-defective JNK1 or a dominant negative MEKK1 the latter being an upstream activator of JNK1. Conversely, u-PAR promoter activity was stimulated by the co-expression of a constitutively active MEKK1 and this induction was antagonized by the inclusion of the kinase-defective JNK1 plasmid. We also determined the biological significance of the JNK1-dependent signaling cascade in regulating u-PAR promoter activity by c-Ha-ras since this oncogene is activated and/or overexpressed in a variety of tumors including ovarian cancer. Transfection of an activated c-Ha-ras into OVCAR-3 cells stimulated u-PAR promoter activity over 20-fold and this could be countered by the individual expression of dominant negative expression constructs to Rac-1, MEKK1 or JNK1. Taken together, these data suggest that the PMA- or c-Ha-Ras-dependent stimulation of u-PAR gene expression requires a JNK1-dependent signaling module and that, at least for PMA, the concurrent stimulation of a JNK1-independent signaling module is also required. Thus, caution should be exercised in invoking linear signaling modules to account for the regulation of inducible gene expression.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Inhibition of the p38 mitogen-activated protein kinase by SB 203580 blocks PMA-induced Mr 92,000 type IV collagenase secretion and in vitro invasion.

Although the p38 mitogen-activated protein kinase (MAPK) has been implicated in signal transduction events, its role in regulating the Mr 92,000 type IV collagenase matrix metalloprotease-9 (MMP-9) and in vitro invasiveness in cancer has not yet been determined. We made the surprising observation that, in a human squamous cell carcinoma cell line (UM-SCC-1), phorbol ester-enhanced MMP-9 secretion and in vitro invasiveness were associated with a strong activation of the p38 MAPK and its downstream target, MAPK-activated protein kinase-2. To determine the role of p38 activation in these events, we investigated the effect of SB 203580, a novel specific p38 inhibitor, on protease expression and in vitro invasion of these cells. We found that inhibition of p38 by SB 203580 resulted in the almost complete reduction of phorbol myristate acetate-induced MMP-9 secretion but not of urokinase-type plasminogen activator secretion. In contrast, the activation of a transiently transfected wild-type MMP-9 promoter by MEKK-1, a specific c-Jun NH2-terminal kinase activator, was only marginally inhibited by the compound, arguing for the specificity of SB 203580. Moreover, phorbol myristate acetate-enhanced in vitro invasion was completely blocked by SB 203580, whereas p38 inhibition had little effect on growth. These findings suggest that activation of p38 may contribute to a more invasive phenotype in vitro, possibly via the expression of MMP-9, and that targeting of p38 using SB 203580 may provide a novel means of controlling invasion of cancers in which this MAPK is activated.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

How many membrane proteins are there?

One of the basic issues that arises in functional genomics is the ability to predict the subcellular location of proteins that are deduced from gene and genome sequencing. In particular, one would like to be able to readily specify those proteins that are soluble and those that are inserted in a membrane. Traditional methods of distinguishing between these two locations have relied on extensive, time-consuming biochemical studies. The alternative approach has been to make inferences based on a visual search of the amino acid sequences of presumed gene products for stretches of hydrophobic amino acids. This numerical, sequence-based approach is usually seen as a first approximation pending more reliable biochemical data. The recent availability of large and complete sequence data sets for several organisms allows us to determine just how accurate such a numerical approach could be, and to attempt to minimize and quantify the error involved. We have optimized a statistical approach to protein location determination. Using our approach, we have determined that surprisingly few proteins are misallocated using the numerical method. We also examine the biological implications of the success of this technique.

Bacterial Proteins↗
PubMed1998

An orthotopic floor-of-mouth cancer model allows quantification of tumor invasion.

OBJECTIVES: To establish an orthotopic murine floor-of-mouth cancer model for the analysis of the role of proteases such as urokinase-type plasminogen activator (u-PA) and the matrix metalloprotease MMP-9 (MMP-9) in in vivo invasion. STUDY DESIGN: Randomized, prospective animal study. METHODS: Two human squamous cell carcinoma cell lines, UM-SCC-1 and 022, were assayed via zymography for their in vitro secretion levels of u-PA and MMP-9. Both cell lines (5 x 10(6) cells) were injected into the cervical subcutaneous tissues of female athymic nude (nu/nu) mice superficial to the mylohyoid muscle. Mice were sacrificed after 30 days, and tumor invasion characteristics were histologically compared. Additional mice were then inoculated with invasive UM-SCC-1 cells and sacrificed 10, 30, and 40 days after inoculation to identify distinct stages of invasion. RESULTS: In vitro secretion levels of MMP-9 and activity of u-PA were higher in UM-SCC-1 cells than in 022 cells. In the in vivo studies, tumors formed from 022 cells were found to be noninvasive, whereas tumors derived from UM-SCC-1 cells progressed through distinct and readily identifiable histologic stages of invasion. These stages included invasion of adjacent muscle layers (mylohyoid, geniohyoid, and genioglossus muscles) and of associated structures (blood vessels, bone, nerve, and regional lymph nodes). A staging system was devised accordingly. CONCLUSION: We developed an in vivo quantitative cancer invasion model that allows determination of the effect of the expression and activity levels of the proteases MMP-9 and u-PA. Tumor invasion occurred in an orderly and stepwise fashion involving muscles and related vascular, nervous, and bony structures of the floor of the mouth and tongue. This orderly invasion allowed the development of a staging system. We anticipate that this model will have wide applicability in the study of in vivo tumor response to a variety of novel therapeutic approaches.

Animals↗
PubMed1998

Aberrant cell division and random FtsZ ring positioning in Escherichia coli cpxA* mutants.

In Escherichia coli, certain mutations in the cpxA gene (encoding a sensor kinase of a two-component signal transduction system) randomize the location of FtsZ ring assembly and dramatically affect cell division. However, deletion of the cpxRA operon, encoding the sensor kinase and its cognate regulator CpxR, has no effect on division site biogenesis. It appears that certain mutant sensor kinases (CpxA*) either exhibit hyperactivity on CpxR or extend their signalling activity to one or more noncognate response regulators involved in cell division.

Bacterial Proteins↗
PubMed1998

Influence of venular prostaglandin release on arteriolar diameter during functional hyperemia.

Indomethacin treatment or removal of the venular endothelium will attenuate functional arteriolar vasodilation in the hamster cremaster muscle. We tested the hypothesis that prostanoid release from venular endothelial cells was responsible for the functional vasodilation of the paired arteriole. The hamster cremaster muscle was prepared for in vivo microscopy and stimulated for 1 minute (10 V, 40 microsec, 1 Hz). Before a second muscle stimulation, the venular endothelium was removed by perfusing the venule with several air bubbles. A third muscle stimulation was performed during prostaglandin inhibition (28 micromol/L indomethacin superfusion). Arterioles (n = 9, 55+/-5 microm) dilated 25+/-4% during the initial muscle stimulation. After removal of the endothelium from the paired venules, there was no effect on resting arteriolar diameters (53+/-4 microm), but the functional arteriolar dilation was attenuated to 15+/-5% (P<.05). The additional indomethacin treatment had a significant effect on resting diameter (50+/-4 microm) but did not alter the magnitude of the functional vasodilation (11+/-4%, P>.05). In a second set of experiments, the order of the experimental protocol was reversed. Muscle stimulation resulted in a 23+/-2% increase in diameter (47+/-2 to 57+/-2 microm). Indomethacin treatment significantly attenuated the functional dilation to 8+/-3% (45+/-2 to 48+/-2 microm). Arteriolar diameter was significantly smaller after disruption of the venular endothelium with air bubbles (40+/-2 microm), but there was no effect on the functional vasodilation, 8+/-3% increase in diameter (to 43+/-2 microm). These results suggest that the arteriolar dilatory response to muscle stimulation is mediated, in part, by prostanoid release from the venular endothelium.

Animals↗