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Results for “Microvessels”

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PubMed2001

Morphologic analysis of microvessels in colorectal tumors with respect to the formation of liver metastases.

BACKGROUND AND OBJECTIVES: Overexpression of VEGF and proliferation of microvessels are strongly related to liver metastases, however, morphologic analyses of microvessels in liver metastases have not been reported. The purpose of the present study was to examine the correlation between liver metastases and the diameters of microvessel lumens in the tumor tissue. METHODS: Fifty-nine patients with liver metastases from colorectal cancers and 112 patients who underwent curative colorectal resection and survived without any recurrence were reviewed. Microvessel density (MVD) and the diameters of the lumens of individual microvessels were assessed. RESULTS: There was a significant difference in terms of the mean MVD of primary tumors between patients with liver metastases and those without liver metastases. The numbers of patients with liver metastases who had microvessels 100-200 microm in diameter and microvessels more than 200 microm in diameter were significantly greater than patients without liver metastases. Microvessels with lumens more than 100 microm in diameter were not detected in the liver metastatic lesion. CONCLUSION: Large microvessels in the primary tumor favor intravasation of cancer cells.

Adult↗

PubMed1993

Model experiments on measuring flow in microvessels using tracers.

Most techniques for measuring plasma or red cell flow velocity within microvessels rely on determining the transit time of a tracer to transverse the distance between two monitoring sites within a vessel. In principle, proper transit time determinations require flow-weighted sampling of the tracer at monitoring sites. In practical application of the tracer technique, however, trace sampling at monitoring sites is not flow-weighted but is area-weighted, and hence elapsed transient time can only be estimated from tracer data. We previously showed theoretically (Microvasc. Res. 40, 394-411, 1990) that the flow velocity determined under these conditions can differ appreciably from the actual mean flow velocity of the carrier fluid within the microvessel. Nevertheless, trace mean flow velocity does approach that of the fluid when tracer velocity is measured past a finite distance from the microvessel entrance. In this study, we examined the tracer measurement of flow experimentally using a physical model. We perfused single glass microvessels and simple fabricated microvessel networks with distilled water at physiological flow rates. Mean tracer velocity (Vd) was determined at several axial locations within the microvessels using injected Evans blue dye. At each location Vd was determined in a manner consistent with usual application of the tracer flow measurement technique. Actual mean flow velocity (Va) was determined from the measured effluent flow rates discharged from each microvessel. Our experimental results confirm the existence of an appreciable velocity measurement error (VME) associated with the tracer technique. The VME behavior was consistent with our original theoretical analysis. Vd was significantly smaller than Va within a finite length of vessel near the entrance, but approached and became equal to Va past this length. Furthermore, even under conditions where the VME was negligible at the end of a parent microvessel, a new and appreciable VME arose within the connecting downstream daughter microvessels. These results underscore that tracer mean flow velocity as obtained in normal implementation of the tracer technique can differ from that for the fluid itself within a microvascular network.

Blood Flow Velocity↗

PubMed1998

Relationship between prostate specific antigen density, microvessel density and prostatic volume in benign prostatic hyperplasia and advanced prostatic carcinoma.

The aim of this study was to investigate the relationship between prostate specific antigen density and prostate volume with microvessel density in patients with benign prostatic hyperplasia and advanced prostatic carcinoma. Sixty-eight patients with benign prostatic hyperplasia and 11 patients with advanced prostatic carcinoma participated in the study. The paraffin blocks of all patients were stained with CD34 by the standard immunohistochemical technique and microvessel density, prostate specific antigen density and prostatic volume were determined. In patients with benign prostatic hyperplasia the mean microvessel density, mean prostate specific antigen density and mean prostatic volume were 74+/-89+/-22.73, 0.12+/-0.10 and 59.97+/-27.0 ml, respectively. There was no correlation between prostate specific antigen density and mean prostatic volume or microvessel density (r = 0.079 and -0.095, respectively). In patients with advanced prostatic carcinoma the mean microvessel density, mean prostate specific antigen density and mean prostatic volume were 147.90+/-47.55, 0.63+/-0.41 and 54.00+/-22.42 ml, respectively. In this group, while there was a good correlation between prostate specific antigen density and microvessel density (r = 0.785), no significant correlation was found between prostatic volume and microvessel density (r = -0.07). There was significant statistical difference in patients with advanced prostatic carcinoma compared to patients with benign prostatic hyperplasia in terms of mean microvessel density (p<0.0001). The findings that there was no correlation between prostatic volume and MVD either in benign prostatic hyperplasia or in prostatic carcinoma suggest that microvessel development is not correlated with prostatic volume but may be correlated with morphology.

Aged↗

PubMed2001

Microvessel density in pituitary adenomas and carcinomas.

Tumor growth depends on several factors, including angiogenesis. Tumors cannot grow if new vessels are not formed to supply the cells with oxygen and other nutrients and to remove waste products. Increased angiogenesis can be correlated with tumor growth and metastatic potential in many tumor types, indicating that neoformation of vessels is a prognostic indicator of tumor behavior. We evaluated microvessel densities in 157 various pituitary adenoma types and seven pituitary carcinomas using immunocytochemistry for CD-34 antigen, a reliable marker of endothelial cells. The lowest percentage of microvessel density was found in growth hormone-producing adenomas, the highest level in pituitary carcinomas. In general, no major correlation was found between MIB-1 index (an indicator of cell proliferation) and microvessel density. The statistical study also demonstrated no gender-dependent changes in the microvessel density of pituitary tumors. Although the microvessel density was not significantly different in relation to invasiveness of pituitary tumors, our results demonstrate a tendency of invasive pituitary tumors to be more highly vascularized than non-invasive ones. Dopamine agonist and long-acting somatostatin analog treatment compared with untreated tumors did not significantly affect microvessel densities. Statistical differences were demonstrated in the microvessel density of macroadenomas between patients older and patients younger than 40 years. Significant differences were also apparent in the microvessel densities between microadenomas and macroadenomas diagnosed in young patients but not in the older age group. The strongly positive correlation observed between microvessel density and age is consistent with the view that age of the host may have an influence on the extent of neovascularization of pituitary adenomas.

Adenoma↗

PubMedDate not supplied

Increased accumulation of cAMP in cerebral microvessels in Alzheimer's disease.

The objective of this study was to compare the adenylyl cyclase-cAMP second messenger system in cerebral microvessels isolated from Alzheimer's patients to that in microvessels from nondemented elderly controls. To evaluate the role of aging separate from the effects of dementia, microvessels from young and aged rodents were also examined. The results of this study indicated that microvessels isolated from autopsy material can be used to evaluate adenylyl cyclase activity. The data showed that cAMP levels, as an index of adenylyl cyclase activity, are significantly (p < 0.02) elevated in microvessels from Alzheimer's disease compared to nondemented elderly controls. Stimulation of adenylyl cyclase by forskolin was comparable in both groups of microvessels. A comparison of unstimulated microvessels from young and aged rodents yielded no significant difference in cAMP levels. These results indicate an increased level of cAMP in the microvessels of Alzheimer's patients with no age-related change demonstrable in rat microvessels.

Adenylyl Cyclases↗

PubMed2004

Microvessel density as a molecular marker for identifying high-grade prostatic intraepithelial neoplasia precursors to prostate cancer.

BACKGROUND: Existing clinical data have shown that high-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precursor to prostate cancer (CaP). Criteria to distinguish HGPIN that progress to CaP from those that do not remain poorly defined. Our objective was to evaluate microvessel density as a molecular marker for distinguishing HGPINs that have the potential of progressing to cancer. MATERIALS AND METHODS: Human prostatic tissue samples were collected randomly from 50 prostatectomy and cystoprostatectomy patients. Formalin-fixed and paraffin-embedded sections were used for immunohistochemical localization of rabbit anti-human von Willebrand factor VIII (vWF) IgG, mouse anti-high molecular weight cytokeratin 34BE-12 in basal cells, and mouse anti-heparan sulphate proteoglycan (HSPG) IgGs in basement membranes associated with benign prostatic hyperplasia (BPH), PIN associated with some BPH (isolated PIN), and PIN associated with CaP. RESULTS: Analysis of immunostaining data showed that PINs could be categorized according to their distributions within and outside 2 standard deviations (SD) of the mean for microvessel density. The average number of microvessels was significantly higher (P < 0.0001) in PINs associated with Gleason score 7 tumors than those associated with Gleason scores 4-6 (P < 0.1328) or 8 and 9 tumors (P < 0.1708). Morphologically, PINs within 2 SD were composed of low- and high-grade type, whereas those outside 2 SD of microvessel density were predominantly of high-grade type. Cytokeratin and HSPG localization patterns also showed differences in PINs found within and outside 2 SD of microvessel density. We found localization of cytokeratin 34BE-12 in basal cells of specimens with BPH alone, isolated PIN, and PIN associated with CaP within 2 SD, whereas many PINs outside 2 SD showed disruptions in cytokeratin localization. The basement membranes of PINs within 2 SD of microvessel density were relatively intact, whereas those outside 2 SD were fragmented. CONCLUSIONS: Our immunostaining data indicates that once HGPIN is found in the initial prostatic biopsy, it should be evaluated for microvessel density by localization of vWF. Our data indicate that characteristics of HGPIN can be augmented by evaluations of cytokeratin and HSPG molecular markers to assess the potential of HGPIN progression to malignancy. When biopsy samples show HGPIN with increased microvessel density and disrupted cytokeratin and HSPG markers, the patient may be a candidate for repeat biopsy. Since our study is limited to 50 prostate tissue samples, we emphasize that our conclusion is tentative and ought to be confirmed in a study with a larger sample size. This is the first report to show that microvessel density may distinguish HGPIN that is a precursor to prostate cancer.

Aged↗

PubMed1998

Thymidine phosphorylase (platelet-derived endothelial cell growth factor), microvessel density and clinical outcome in hepatocellular carcinoma.

BACKGROUND/AIMS: Angiogenesis plays an important role in tumor growth and metastasis. It is regulated by angiogenic factors. Thymidine phosphorylase (platelet-derived endothelial cell growth factor) is one such factor. Although the significance of platelet-derived endothelial cell growth factor has been studied for several types of tumor, the expression of platelet-derived endothelial cell growth factor and its correlation with microvessel density or clinicopathological factors in hepatocellular carcinoma are unknown. We evaluated microvessel density and platelet-derived endothelial cell growth factor expression in hepatocellular carcinoma to determine whether microvessel density and platelet-derived endothelial cell growth factor expression are correlated with the clinicopathological factors of hepatocellular carcinoma. METHODS: Using immunohistochemical staining with anti-platelet-derived endothelial cell growth factor antibody and the ELISA method, we evaluated the correlation among platelet-derived endothelial cell growth factor expression, microvessel density and clinicopathological factors in 84 hepatocellular carcinoma patients. Microvessels were stained with anti-human von Willebrand factor (anti-Factor VIII) and anti-CD34. RESULTS: In the surrounding liver, there was a significant correlation between microvessel density and platelet-derived endothelial cell growth factor expression (p=0.002), and hepatitis C virus-positive livers had higher microvessel densities than otherwise (p=0.003). However, this correlation was not found for hepatocellular carcinoma, but hepatitis C virus-positive tumors had higher expression of platelet-derived endothelial cell growth factor (p=0.018). Microvessel density in hepatocellular carcinoma obtained by Factor VIII staining inversely affected the recurrence-free survival rate (p=0.0416), but the microvessel density by CD34 staining was not a significant predictor. CONCLUSIONS: This study indicates that platelet-derived endothelial cell growth factor may not be a major regulator of angiogenesis of hepatocellular carcinoma, but this enzyme may play an important role in hepatocarcinogenesis cooperating with hepatitis C virus. Also, the density, not of sinusoid-like vessels, but of larger vessels in hepatocellular carcinoma could be a prognostic factor for hepatocellular carcinoma.

Antigens, CD↗

PubMedDate not supplied

Inflammatory factors are elevated in brain microvessels in Alzheimer's disease.

In Alzheimer's disease (AD) inflammatory processes occur in pathologically vulnerable brain regions. The objective of this study is to compare both the release and the presence of microvessel-associated cytokines in vessels isolated from the brains of AD patients to microvessels from control brains. Microvessels are isolated from the cortices of AD patients and age-matched controls, without evidence of neurodegenerative disease. Inflammatory factors in the media are quantitated by ELISA and microvessel-associated mediators assessed by Western blot. Our results demonstrate that unstimulated AD microvessels release significantly higher levels of interleukin-1beta-(IL-1beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) compared to non-AD microvessels. Levels of microvessel-associated monocyte chemoattractant protein (MCP-1) and IL-1beta are high in AD-derived microvessels, but not detectable in non-AD microvessels. These results suggest that the cerebral microcirculation contributes inflammatory mediators to the milieu of the AD brain and may be involved in the pathogenesis of neuronal injury and death in this disorder.

Aged↗

PubMed2002

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis.

In order to determine whether angiogenesis is a prognostic marker in lung cancer, we performed a systematic review of the literature to assess the prognostic value on survival of microvessel count in patients with lung cancer. Published studies were identified by an electronic search in order to aggregate survival results, after a methodological assessment using a quality scale designed by the European Lung Cancer Working Party. To be eligible, a study had to deal with microvessel count assessment in lung cancer patients on the primary site and to provide survival analysis according to microvessel count expression. Microvessel count has been assessed on surgical samples by immunohistochemistry using factor VIII in 14 studies, CD34 in 10 and CD31 in eight. Respectively 1866, 1440 and 1093 non-small cell lung cancer patients were considered. The overall median quality scores were respectively 52, 59 and 59% for studies assessing microvessel count via factor VIII, CD34 and CD31, without significant difference between studies evaluable or not for meta-analysis nor between studies with significant or non significant results. Seven 'factor VIII' studies, nine 'CD34' and seven 'CD31' provided sufficient data allowing a meta-analysis on survival and were evaluable for results aggregation. This showed that a high microvessel count in the primitive lung tumour was a statistically significant poor prognostic factor for survival in non small cell lung cancer whatever it was assessed by factor VIII (HR: 1.81; 95% CI: 1.16-2.84), CD34 (HR: 1.99; 95% CI: 1.53-2.58) or CD31 (HR: 1.80; 95% CI: 1.10-2.96). Variations in survival among the individual studies can be explained in addition to patients selection criteria by the heterogeneous methodologies used to stain and count microvessels: different antibody clones, identification of 'hotspots', Weidner or Chalkey counting method, cut-off selection. Microvessel count, reflecting the angiogenesis, appears to be a poor prognostic factor for survival in surgically treated non small cell lung cancer but standardisation of angiogenesis assessment by the microvessel count is necessary.

Humans↗

PubMed1996

Docosahexaenoic acid is a major n-3 polyunsaturated fatty acid in bovine retinal microvessels.

The aim of this study was to purify microvessels from bovine retina and also to cultivate bovine retinal endothelial cells (BRECs) or intramural pericytes, to determine their fatty acid composition. Microvessels were obtained after Dounce homogenization of the retina followed by centrifugation on albumin cushion and finally microvessels in the pellet were trapped on a 100-microns nylon filter. Contamination of microvessel preparations by neuronal tissue, assessed after both microscopic examination and western blotting with a monoclonal antibody raised against rhodopsin, was minor. In the entire bovine retina, docosahexaenoic acid (DHA) represented 23.3% of the total fatty acids and there was about three times less arachidonic acid (AA) (8.2%) than DHA. In contrast, DHA and AA levels were almost equivalent in the retinal microvessels with approximately 10% of total fatty acids. When compared with intact microvessels, the DHA proportion of confluent monolayers of both BRECs or pericytes in primary cultures dropped to approximately 2% of the total fatty acids, whereas AA was unchanged. Culture medium supplementation with unesterified DHA (10 microM) restored the DHA proportion of BRECs close to the microvascular value at the expense of linoleic acid without affecting AA very much. In contrast, DHA supplementation in pericytes increased the DHA proportion of these cells at the expense of AA. In conclusion, DHA of intact microvessels represented 10% of the total fatty acids, which was close to the AA proportion. Mild DHA supplementation of BRECs or pericytes in primary cultures restored their DHA proportion to the original microvessel value. This high percentage of polyunsaturated fatty acids in retinal microvessels should allow us to test the hypothesis that oxidation products derived from these fatty acids may be involved in the pathogenic process leading to diabetic retinopathy.

Animals↗

PubMed2001

HER2 signaling--induced microvessel dismantling.

BACKGROUND: The human epidermal growth factor receptor 2 protein (HER2) signaling in breast cancer imparts a metastatic advantage to the cell, likely by regulating gene expression. The HER2 signaling up-regulates angiopoietin-2 (Ang-2), which disrupts endothelial cell (EC) adherens junctions. We postulated that HER2 signaling may facilitate angioinvasion by disrupting microvessel integrity. METHODS: Rat microvessels, embedded in collagen, were grown into capillary networks and cocultured with MCF-7 or HER2 overexpressing MCF-7 (HER) to test for microvessel breakdown. We quantitated this effect by determining the cumulative length of intact microvessels. Other experiments used Herceptin- or heregulin beta 1-pretreated MCF-7 cells to modulate HER2 signaling, or soluble Tie-2/Fc receptor fusion protein (sTie2) to sequester tumor-cell released Ang-2. RESULTS: The MCF-7 cells induced a time-dependent loss of microvessel integrity. At 12 hours, HER cells induced a 90% reduction in cumulative length (P <.05). Pretreatment with Herceptin reduced whereas heregulin beta 1 augmented microvessel dismantling (P <.01). Sequestration of Ang-2 significantly, though not dramatically, reduced the MCF-7 cell induction of microvessel dismantling (P <.01). CONCLUSIONS: We show that HER2 signaling in breast cancer cells leads to induction of microvessel dismantling, which may open a portal for angioinvasion. It appears that Ang-2 affects this mechanism, although other factors also function in microvessel dismantling.

Angiopoietin-1↗

PubMed1996

Preferential dilation of large coronary microvessels by the mononitrates SPM-4744 and SPM-5185.

A novel aspect of the pharmacodynamic action of nitroglycerin is that it is a potent dilator of larger coronary arteries, yet it dilates smaller coronary microvessels submaximally and only in high concentrations. We sought to determine whether this property was shared by other organic nitrates. The effects of two mononitrates. SPM-4744 and SPM-5185 (the latter of which possesses a thioester in its structure), on coronary microvessels of different sizes were studied. Large (200-microns diameter) and small ( < 100-microns diameter) porcine coronary microvessels were studied in vitro while pressurized in a no-flow state. After constriction with the thromboxane analogue U46619, maximal dilations (as a percent of preconstricted tone at the highest applied concentration, 10 microM) of small coronary microvessels were 18 +/- 3 and 16 = 2% in response to SPM-4744 and SPM-5185, respectively. The dilations of larger coronary microvessels to SPM-4744 and SPM-5185 were 55 +/- 5 and 43 +/- 6%, respectively (both p < 0.001 vs. the small vessel responses). This pattern of differential vasodilatation of large and small coronary microvessels was similar to that produced by nitroglycerin. In contrast, sodium nitroprusside produced equivalent degrees of vasodilation of small and large coronary microvessels. Additional experiments demonstrated that both SPM compounds produced dilation of the coronary microcirculation in isolated rat heart and relaxed isolated segments of rat aortic rings only in high ( > or = 1 microM) concentrations. These data demonstrate that the organic mononitrates are similar to nitroglycerin in their selectivity for larger coronary microvessels and produce only minimal dilation of coronary microvessels < 100 microM in diameter.

Animals↗

PubMed1999

Endothelial cell shrinkage increases permeability through a Ca2+-dependent pathway in single frog mesenteric microvessels.

1. We tested whether calcium (Ca2+)-dependent mechanisms were essential for our previous observation that a change in the endothelial cell (EC)-extracellular matrix (ECM) attachment caused an increase in microvessel hydraulic permeability (Lp) after exposure to hypertonic solutions in single perfused mesenteric microvessels in pithed frogs (Rana pipiens). 2. In microvessels where integrin-dependent EC-ECM attachments were disrupted by pretreatment with the peptide Gly-Arg-Gly-Asp-Thr-Pro (GRGDTP; 0.3 mmol l-1), we measured microvessel Lp after exposure to hypertonic solutions under experimental conditions that reduced Ca2+ influx into endothelial cells. 3. High K+ solutions (59.7 and 100 mmol l-1 K+) were used to depolarize the endothelial membrane and therefore to reduce the electrochemical driving force for Ca2+ influx through conductive Ca2+ channels. These solutions abolished the increase in Lp caused by hypertonic solutions in the microvessels pretreated with GRGDTP. 4. We previously suggested that the removal of albumin from the perfusate may reduce EC-ECM attachment because hypertonic solutions increased the Lp of microvessels above that due to removal of albumin alone. This additional increase in Lp was attenuated by the 59.7 mmol l-1 K+ solution and was completely abolished by the 100 mmol l-1 K+ solution. 5. Bumetanide, an inhibitor of the Na+-K+-2Cl- co-transporter and one of the mechanisms of regulatory volume increase after exposure to hypertonic solutions in endothelial cells, did not change the response of microvessels to high K+ solutions. 6. Our findings indicate that Ca2+ entry into endothelial cells via passive conductance channels is necessary to increase microvessel Lp after exposure to hypertonic solutions in microvessels where EC-ECM attachments are disrupted.

Albumins↗

PubMed1992

Vasomotor properties of porcine endocardial and epicardial microvessels.

We sought to compare the sensitivity of endocardial and epicardial microvessels to several important neurohumoral substances. Porcine endocardial microvessels (86-200 microns diam) from the anterior papillary muscle and epicardial microvessels of similar size from the left anterior descending distribution were studied in a pressurized state using an in vitro microvessel-imaging apparatus. Endothelium-dependent relaxations to bradykinin, ADP, A23187, and to the endothelium-independent vasodilator nitroprusside were identical between endocardial and epicardial microvessels. In contrast, the sensitivity of endocardial microvessels to adenosine was substantially greater than that of epicardial microvessels (ED50s of -6.59 +/- 0.05 vs. -5.66 +/- 0.11, P less than 0.001, endocardial vs. epicardial, respectively), although adenosine caused 100% relaxation of both groups of vessels at the highest concentrations. Adenosine vasorelaxation was not affected by inhibition of cyclooxygenase by indomethacin (1 microM) or depletion of guanosine 3',5'-cyclic monophosphate by LY 83583 (1 microM). Forskolin dilated both endocardial and epicardial vessels completely but was more potent in endocardial vessels. These data show that endocardial and epicardial microvessels exhibit similar sensitivity to most vasodilator agents. Endocardial microvessels, however, are more sensitive to both adenosine and forskolin. The enhanced responsiveness to adenosine may be related to adenosine 3',5'-cyclic monophosphate-mediated mechanisms and may have important implications regarding regulation of myocardial perfusion in deeper subendocardial layers.

Adenosine↗

PubMed1996

Ca2+ entry through conductive pathway modulates receptor-mediated increase in microvessel permeability.

We investigated the relationship between receptor-mediated increases in cytoplasmic Ca2+ concentration ([Ca2+]i) and increased microvessel permeability. In individually perfused venular microvessels of frog mesentery exposed to 10 microM ATP, [Ca2+]i increased from 59 +/- 7 to 172 +/- 21 nM within 1 min and then fell back toward control values. The corresponding peak increase in the hydraulic conductivity (Lp) of the microvessel wall was 5.7 +/- 0.5-fold relative to control. After removal of extracellular Ca2+, there was no significant increase in Lp, and the initial increase in [Ca2+]i was attenuated but not abolished. Depolarization of the endothelial cell membrane with high-K+ Ringer solution reduced the peak increase in [Ca2+]i to 106 +/- 7 nM and attenuated the increase in Lp 1.8 +/- 0.4-fold. The results conform to the hypothesis that Ca2+ entry into endothelial cells is required for acute increase in venular microvessel permeability by inflammatory agents and that the pathway for Ca2+ entry has the properties of a passive conductance pathway. Similar conclusions were reached in previous experiments in frog microvessels exposed to Ca2+ ionophores and perfusates with no plasma proteins. In venular microvessels of hamster mesentery exposed to ATP and bradykinin, a similar pathway for Ca2+ entry was demonstrated in the present experiments. We did not measure permeability changes in hamster microvessels in this study, but these microvessels respond to histamine and ionophores with a transient increase in permeability to macromolecules similar to that measured in frog microvessels [Am. J. Physiol. 268 (Heart Circ. Physiol. 37): H1982-H1991, 1995].

Adenosine↗

PubMed1980

Isolated brain microvessels: preparation, morphology, histamine and catecholamine contents.

A method for the rapid preparation of parenchymal microvessels from rat, rabbit and bovine brains is described. Light and electron microscopic examination of the isolated microvessels showed the smooth muscle and endothelial cells to be intact and substantially free of neutrophil contamination. The observation of 0.2 to 2.0 micron electron dense granules in the adventitial space associated with some of the isolated arteriolar elements and the identification of histamine in microvessel extracts is suggestive of the presence of mast cells in the microvessel preparations. Age-dependent changes in histamine content and an increased histamine content in microvessels from hypertensive rats were noted. Using a sensitive radioenzymatic assay, the catecholamine (CA) contents of microvessels isolated from cow, rat and rabbit were measured. The total CA contents of all microvessel preparations were small (< 0.35 microgram g-1) with norepinephrine being the predominant CA present. A large ratio of dopamine to norepinephrine was found in microvessels from rat and bovine brain. The possible origins of the CAs present in the isolated microvessels are discussed.

Animals↗

PubMed1999

Different effects of protamine on canine coronary microvessel and conductance arteries: evidence of hyperpolarizing factor release.

BACKGROUND: Protamine administration may lead to systemic hypotension, perhaps because of vasodilatation produced by endothelial nitric oxide. This study compared release of vasoactive substances from canine coronary microvessels with that from paired conductance arteries. METHODS: Microvessels were mounted in a videoscopic no-flow system, and circumflex arteries were studied in organ chambers; both were induced to contract by endothelin-1. RESULTS: Protamine (10 to 160 micrograms/mL) produced concentration-dependent relaxation in both microvessel and conductance arteries (46% +/- 14% maximal relaxations in microvessel and 82% +/- 15% in conductance arteries, n = 10 each). Removal of the endothelium abolished this relaxation (P < .05, n = 6). Indomethacin (10(-5) mol/L) did not alter the relaxation in either group (51% +/- 10% in microvessel and 103% +/- 7% in conductance arteries, n = 6 each). NG-monomethyl-L-arginine (L-NMMA, 10(-4) mol/L) attenuated relaxation in conductance arteries (38% +/- 12%, P = .04, n = 6) but had no effect on microvessel arteries (58% +/- 10%, n = 6). Tetraethylammonium chloride (10(-3) mol/L), an inhibitor of voltage-dependent potassium channels, had no effect on conductance arteries (103% +/- 9%, n = 6) but abolished relaxation in microvessels (-25% +/- 11%, P = .03, n = 6). CONCLUSIONS: Protamine sulfate causes endothelium-dependent relaxation in microvessel and conductance arteries in the heart by different mechanisms--that is, by nitric oxide release in conductance arteries and by endothelium-derived hyperpolarizing factor (EDHF) release in microvessels. This is the first description of the release of EDHF in response to protamine administration.

Animals↗

PubMed1989

Eicosapentaenoic acid metabolism in brain microvessel endothelium: effect on prostaglandin formation.

Mouse brain microvessel endothelial cells convert eicosapentaenoic acid (EPA) to prostaglandin (PG) E3, PGI3, and several hydroxy fatty acid derivatives. Similar types of products are formed by these microvessel endothelial cells from arachidonic acid. The formation of PGI2 and PGE2 is reduced, however, when the brain microvessel endothelial cultures are incubated initially with EPA. Exposure to linolenic or docosahexaenoic acid also decreased the capacity of these microvessel endothelial cells to form PGI2 and PGE2, but the reductions were smaller than those produced by EPA. Like the endothelial cultures, intact mouse brain microvessels convert EPA into eicosanoids, and incubation with EPA reduces the subsequent capacity of the microvessels to produce PGI2 and PGE2. Brain microvessel endothelial cells took up less EPA than arachidonic acid, primarily due to lesser incorporation into the inositol, ethanolamine, and serine glycerophospholipids. By contrast, considerably more EPA than arachidonic acid was incorporated into triglycerides. These findings suggest that the microvessel endothelium may be a site of conversion of EPA to eicosanoids in the brain and that EPA availability can influence the amount of dienoic prostaglandins released by the brain microvasculature. Furthermore, the substantial incorporation of EPA into triglyceride suggests that this neutral lipid may play an important role in the processing and metabolism of EPA in brain microvessels.

Animals↗