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Aminergic and cholinergic innervations of the spinal cord blood vessels of cats. A histochemical study.

The distribution patterns of aminergic and cholinergic nerve fibers in the feline spinal cord blood vessels were studied by means of amine histofluorescence and acetylcholinesterase (AChE) staining. These patterns were compared with those of the cerebral blood vessels. The anterior spinal artery had a dense network of aminergic and AChE-positive (probably cholinergic) nerve fibers. The posterior spinal vein, in contrast, exhibited only aminergic nerve fibers. Small intraparenchymal blood vessels in the spinal cord also had strongly fluorescent (probably peripheral) aminergic nerve fibers, as well as pial spinal blood vessels. This was a characteristic feature in the spinal cord. The distribution pattern and the density of these two sorts of nerve fibers in the anterior spinal artery varied widely with the individual segment of the spinal cord. The thoracic spinal cord had the lowest number of these nerve fibers of any part of the spinal cord. This fact may explain why the thoracic spinal cord is most susceptible to ischemic change.

Acetylcholinesterase↗

Relation in rat hind-limb blood vessels between nervous vasomotor tone and the response to vasoconstrictor drugs.

When the nervous component of the vasomotor tone of the blood vessels of the innervated rat hind limb perfused with blood was reduced by ganglion blockade, by section of the nerves to the hind limb, or by the indirect effect of drugs, the vasoconstrictor response of the blood vessels to noradrenaline was immediately increased. This increased peripheral response was observed only when the blood perfusing the hind limb was from the same animal or from a genetically similar animal. Reduction of the nervous component of the vasomotor tone also increased the constrictor response of the hind-limb blood vessels to adrenaline, ephedrine, tyramine and 5-hydroxytryptamine, but did not increase the response to angiotensin, vasopressin or S-methyl isothiourea. Pre-treatment with reserpine increased the hind-limb response to noradrenaline but reduced the response to ephedrine, tyramine and 5-hydroxytryptamine. The results suggest that, in rats, activity in the sympathetic nervous system directly influences the reactivity of peripheral blood vessels to noradrenaline and other sympathomimetic drugs.

Animals↗

Glomeruloid blood vessels in ethylnitrosourea-induced rat gliomas. Histological and immunohistochemical studies.

Glomeruloid blood vessels (GBVs), a characteristic histological feature of most human malignant gliomas, were recognized with high incidence in autochthonous rat gliomas induced by transplacental administration of ethylnitrosourea. To evaluate some of the biological properties of these GBVs, we carried out a study using histological methods and immunohistochemical staining for glial fibrillary acidic protein, factor VIII-related antigen (VIII Ag) and bromodeoxyuridine (BrdUrd). Of 22 animals with large, massively growing gliomas in the CNS, GBVs including conglomerate aggregations of small blood vessels with endothelial hyperplasia and strong VIII Ag expression were observed in 13 large gliomas histologically consisting of primitive neuroepithelial neoplasms (PNN; so called ependymoma) and mixed-type gliomas in combination with astrocytoma and PNN or anaplastic astrocytoma. The anaplastic gliomas in our series were devoid of GBVs. These findings indicate that GBV formation takes place in a histological variety of experimental gliomas. Furthermore, the GBVs were frequently associated with the vasculo-mesenchymal stroma in the parent gliomas, suggesting an intimate relationship with the morphogenesis of GBVs. In addition, it was shown that the GBVs had a higher BrdUrd-labelling index than that of other blood vessels in gliomas and also that of neoplastic cells in most parent gliomas, except for anaplastic gliomas. Based on these results, the possible mechanism of GBV morphogenesis is discussed with regard to the roles of macromolecules in the induction and regulation of GBVs.

Animals↗

Sensory nerves determine the pattern of arterial differentiation and blood vessel branching in the skin.

Nerves and blood vessels are branched structures, but whether their branching patterns are established independently or coordinately is not clear. Here we show that arteries, but not veins, are specifically aligned with peripheral nerves in embryonic mouse limb skin. Mutations that eliminate peripheral sensory nerves or Schwann cells prevent proper arteriogenesis, while those that disorganize the nerves maintain the alignment of arteries with misrouted axons. In vitro, sensory neurons or Schwann cells can induce arterial marker expression in isolated embryonic endothelial cells, and VEGF(164/120) is necessary and sufficient to mediate this induction. These data suggest that peripheral nerves provide a template that determines the organotypic pattern of blood vessel branching and arterial differentiation in the skin, via local secretion of VEGF.

Animals↗

Mitochondrial angiopathy in cerebral blood vessels of mitochondrial encephalomyopathy.

We studied cerebral blood vessels of two autopsied patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). All the main cerebral arteries in the proximal portion at the brain base and more distal portion at the cortical surface, as well as within the brain parenchyma were examined by electron microscopy. There was a striking increase in number of mitochondria in the smooth muscle and endothelial cells, which were most prominent in the pial arterioles and small arteries up to 250 micron in diameter and less frequent and severe in the larger pial arteries and intracerebral arterioles and small arteries. These vascular changes have not hitherto been described in MELAS, or in other disorders affecting blood vessels of the brain and other organs. It is suggested that the vascular changes are caused by primary mitochondrial dysfunction in the vascular smooth muscle and endothelial cells of the brain and that they constitute the pathogenic base of the brain lesions and their unusual distribution pattern in MELAS.

Adolescent↗

Blood vessel uptake and metabolism of organic nitrates in the rat.

Recent reports have suggested that the unusual pharmacokinetics observed for nitroglycerin (NTG) and isosorbide dinitrate (ISDN) may be partially explained by extensive uptake and/or metabolism of these drugs by vascular and other extrahepatic tissues. Using the rat as an animal model, this hypothesis was examined by in vivo intravessel NTG and [14C]ISDN infusion and injection into various vessel segments, viz. the femoral vein, inferior vena cava [IVC: lower, middle and upper) and the aorta. NTG and [14C]ISDN concentrations were determined in these blood vessels and in plasma. Blood vessel segments nearest the input site had the greatest amounts of nitrate, whereas segments further away from the input site had progressively less nitrate, with the exception of aorta, which appeared to take up NTG less extensively, on a per weight of vessel basis, than the IVC. Blood vessel NTG concentrations (nanogram per gram) were generally higher (10-fold) and declined about twice as slowly as NTG plasma concentrations (nanograms per milliliter). [14C]NTG and [14C]ISDN were also incubated with cofactors in IVC, aorta, abdominal muscle, lung and liver. The amounts of nitrate metabolites formed from parent drug were larger in each extrahepatic tissue incubation than in the controls (P less than .05). The results are consistent with the hypothesis that vascular and other extrahepatic tissues can take up and/or metabolize organic nitrates. The data appear to provide a partial explanation for the large systemic clearance seen with nitrates and appear consistent with existing mechanistic hypotheses for the vascular action of these compounds.

Animals↗

Lymph and blood vessel architecture in benign and malignant prostatic tissue: lack of lymphangiogenesis in prostate carcinoma assessed with novel lymphatic marker lymphatic vessel endothelial hyaluronan receptor (LYVE-1).

PURPOSE: Due to the lack of specific markers the analysis of lymphatic vessel density (LVD) has been almost impossible in the past. We report the novel specific marker for lymphatic endothelium, lymphatic vessel endothelial hyaluronan receptor (LYVE-1), in prostatic, benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissue. Normal blood vessels were additionally quantified in BPH and PCa. MATERIALS AND METHODS: LYVE-1 lymphatics (LVD) and CD34 blood vessels were assessed in 20 paraffin sections of BPH and 50 of PCa tissue by immunohistochemistry in a standardized experimental setting. The regions of PCa, periphery of the tumor and nontumorous regions of the PCa specimens, and BPH tissue were evaluated. Double staining was done (LYVE-1/CD34). Acquired data were interrelated and compared to the pathological parameters of the specimens. RESULTS: Double staining revealed numerous CD34 blood vessels but only a few LYVE-1 lymphatic vessels in BPH and PCa sections. Mean LVD +/- SD was distinctly lower (0.55 +/- 0.93) in PCa tissue than in tumor periphery (2.45 +/- 1.93) and nontumorous (3.16 +/- 2.23) tissue (p <0.0001). Maximum LVD was observed in BPH (7.17 +/- 3.61), which differed markedly from nontumorous areas of PCa specimens (p <0.001). In contrast to LVD, significantly more blood vessels were found in PCa (116.00 +/- 39.25) than in BPH (60.30 +/- 19.34) tissue (p <0.001). CONCLUSIONS: LYVE-1 is a specific lymphatic endothelial marker in benign and malignant prostate tissues. It is a useful new marker for the investigation of lymphatics. To our knowledge we report the immunohistochemical visualization and quantification of lymphatic vessels in prostatic tissue for the first time. In contrast to the stimulated angiogenesis of blood vessels in PCa, the destruction of lymphatic vessels occurs rather than lymphangiogenesis.

Antigens, CD34↗

Structure of small blood vessels in the testes of infertile men.

In the testis, 'hyalinization' of the lamina propria of seminiferous tubules is often accompanied by similar changes within the walls of testicular blood vessels. The aim of our study was to investigate the structure of small blood vessels in hyalinized human testes by means of immunohistochemistry, electron microscopy and image analysis methods. Results of immunohistochemical analysis indicated that, despite hyalinization, testicular small blood vessels retained positive immunostaining for desmin and actin. Their basement membranes remained immunopositive for collagen IV and laminin. No proliferative (Ki-67) activity was observed in the blood vessel walls in testes from both control and infertile men. P-170 glycoprotein was found to be expressed only in primary spermatocytes. No difference in expression and localization of this antigen was observed between control and affected testes. Electron microscopy revealed a number of testicular arterioles with a notably narrow lumen due to enlarged endothelial cells in infertile men. Such arterioles also had a thickened subendothelial layer and an abundant tunica adventitia rich in connective tissue fibres and ground substance. Some venules in hyalinized testes displayed increased connective fibres and ground substance in the subendothelial layer, between the smooth muscle cells of the tunica media and the tunica adventitia. However, no changes were found in the capillary network, when compared to controls. Image analysis data showed a statistically significant increase in the surface of tunica intima and adventitia of arterioles and tunica media of venules. It is concluded that hyalinization mostly affects testicular arterioles and venules, but not capillaries. Our immunohistochemical data indicate that the 'nature' and/or extent of hyalinization in testicular small blood vessels differs from that described previously for the lamina propria of seminiferous tubules.

Adult↗

5-HT1B-receptors and vascular reactivity in human isolated blood vessels: assessment of the potential craniovascular selectivity of sumatriptan.

AIMS: 5-HT1B-receptor mediated vasoconstriction of cranial arteries is a potential mechanism by which 5-HT1B/1D-receptor agonists such as sumatriptan produce their antimigraine effects. 5-HT1B-receptors exist in other blood vessels which may give rise to unwanted vascular effects. Therefore we examined the distribution of 5-HT1B-receptor immunoreactivity (i.r.) in human blood vessels (including target and nontarget vessels) and confirmed the functionality of this receptor protein, by comparing the vasoconstrictor effects of sumatriptan and 5-HT (the endogenous ligand) in isolated vessels. METHODS: Blood vessels (middle meningeal, pial, temporal and uterine arteries and saphenous veins) were obtained from surgical patients (with consent). Sections of the vessels were prepared for routine immunohistochemical studies using specific 5-HT1B- and 5-HT1D-receptor antibodies. For functional studies, ring segments of the vessels were mounted in organ baths for isometric tension recording. RESULTS: 5-HT1B-receptor i.r. was detected on the smooth muscle layer in middle meningeal, pial and uterine arteries and in saphenous vein and sumatriptan produced contractions in these vessels with potency values (mean pEC50) of 7.00, 7.08, 6.44 and 6.61, respectively, the magnitude of contraction was greatest in the cranial arteries with Emax values of 100.7, 60.3, 23.0 and 35.9%, respectively (expressed as a percentage of the reference agonist 45 mm KCl). 5-HT1B-receptor i.r. was not detected in temporal artery and sumatriptan had no effect in this artery. 5-HT1D-receptor i.r. was not detected in any of the vessels studied. CONCLUSIONS: Sumatriptan can evoke vasoconstriction in antimigraine target vessels and also in nontarget vessels through an action at 5-HT1B-rcceptors. Sumatriptan acts preferentially to cause contraction in human cranial arteries compared with the other blood vessels we examined and this effect is likely to be shared by other drugs of this class.

Cerebral Veins↗

Effect of experimental tooth movement on nerve fibres immunoreactive to calcitonin gene-related peptide, protein gene product 9.5, and blood vessel density and distribution in rats.

The effect of experimental tooth movement on nerve fibers immunoreactive to calcitonin gene-related peptide (CGRP) and to protein gene product (PGP) 9.5 were studied, as well as the coincidence of these responses with changes in blood vessel density and distribution in the periodontal ligament (PDL) and pulp of young Wistar rats. The first right maxillary molar was moved mesially by an orthodontic appliance for 3, 7, 14 and 21 days. Sagittal and horizontal serial sections were incubated alternately with antibodies to CGRP, PGP 9.5 and laminin. Nerve and blood vessel density and distribution between the experimental and control sides were compared in the apical and cervical PDL, and in root and coronal pulp. The most pronounced changes occurred in the 7 day group. CGRP and PGP 9.5 immunoreactive nerves in the apical PDL showed increased density, being distributed towards the alveolar bone and frequently found in bone resorption lacunae. Numerous nerve fibres were often present adjacent to hyalinized tissue, but were never found near or within root resorption lacunae. Nerve sprouting was also present both in the root and coronal pulp. Increased nerve and blood vessel density generally coincided with each other. At day 14, periodontal nerves and blood vessels were still disorganized compared with the controls. Tissues near cellular cementum and root resorption lacunae were consistently devoid of nerve fibres. After 21 days, PDL nerve and blood vessel density and distribution were nearly at control level. However, nerve fibres were regularly found inside root resorption areas. In conclusion, experimental tooth movement induces dynamic changes in density and distribution of periodontal and pulpal nerve fibres, indicating their involvement in both early stages of periodontal remodelling and later in the regenerative processes of the PDL, generally occurring in concerted action with modulation of blood vessels.

Alveolar Process↗

[Electron microscopic observations of blood vessels in ependymoma].

The findings of an ultrastructural study of the blood vessels and their surrounding structures in ependymoma are demonstrated. Six surgically removed cases of ependymoma are investigated. The lumen of the blood vessels, especially in vascular rosettes is often wider than those of normal brain capillaries. The endothelial cells are structurally varied, but sometimes attenuated in many areas. Also, they often have several fenestrations. Moreover, they have increased pinocytotic vesicles and filaments, and contain occasional Weibel-Palade bodies, multivesicular bodies and other cytoplasmic organelles. The perivascular space is often wide, especially in intraspinal ependymoma, and filled with multiple layers of basal laminae permeated by electron, dense fluids. There are also collagenous fibers and Luse bodies. Basal lamina covering tumor cell surfaces is more distinct than other basal laminae. The tumor cells facing the blood vessel interestingly show structures similar to those of astrocytic vascular feet. The fenestration in the endothelial cells probably has an important role in the increased vascular permeability of ependymoma.

Basement Membrane↗

Platelet and blood vessel arachidonate metabolism and interactions.

Exogenous arachidonate addition to intact platelets, in the absence or the presence of blood vessel microsomes, results in the production of thromboxane B(2) (the stable degradation product of thromboxane A(2)) only. Prostaglandin (PG) endoperoxides are released from intact platelets only when thromboxane synthetase is inhibited. Thus, addition of exogenous arachidonate to imidazole-pretreated platelets in the presence of bovine aorta microsomes (source of prostacyclin synthetase) results predominantly in the synthesis of 6-keto-PGF(1alpha) (the stable degradation product of prostacyclin). Strips of intact aorta were removed from aspirin-treated rabbits, thus the isolated blood vessels were unable to convert endogenous or exogenous arachidonate to prostacyclin. Human platelets, with [(14)C]arachidonate-labeled phospholipids, adhered to the blood vessel segments and released some thromboxane B(2). The subsequent addition of thrombin facilitated the release of endogenous arachidonate and thromboxane, but no labeled 6-keto-PGF(1alpha) was detectable. There is therefore no direct chemical evidence of PG-endoperoxide release from human platelets during either aggregation or adhesion, which therefore precludes the possibility that blood vessels use platelet PG-endoperoxide for prostacyclin synthesis. Imidazole inhibited the thromboxane synthetase in the labeled platelets, and thereafter thrombin stimulation resulted in the release of platelet-derived, labeled PG-endoperoxides that were converted to labeled prostacyclin by the vascular prostacyclin synthetase. The latter result suggests a potential antithrombotic therapeutic benefit might be achieved using an effective thromboxane synthetase inhibitor.

Animals↗

Extracellular matrix molecules influence innervation density in rat cerebral blood vessels.

We have investigated the contribution of the acellular component (i.e., the extracellular matrix, or ECM) in determining the innervation density of peripheral target tissue, and the possible involvement of ECM molecules in age-related axonal atrophy. We addressed this issue using cerebral blood vessels where both the overall density and the density of sympathetic innervation decrease by 50% in aged rats. In order to study the capacity of the ECM to influence pattern and density of innervation, cerebral blood vessels from young (6 weeks) and old (24 months) rats were repeatedly freeze-thawed to kill the cellular component of the vessel wall before transplantation in oculo into young host rats. After 4 weeks, the nature and degree of reinnervation of transplants by host nerves was studied by quantitative immunohistochemistry using PGP9.5 (a general neuronal marker) or CGRP (calcitonin gene-related peptide, a sensory marker), or catecholamine histochemistry using the glyoxylic acid technique to visualise noradrenergic sympathetic nerves. The density of reinnervation was measured by computerized image analysis. The PGP-immunoreactive reinnervation on old transplanted cerebral blood vessels was significantly less dense compared to young ones. However, nerve density on both young and old transplants was lower than on control, ex vivo blood vessels. CGRP-positive nerves on both young and old transplants were sparse, but similar to control tissues, whereas catecholamine-containing nerves were very sparse on all transplants, and significantly less than on control blood vessels. These results suggest that alterations occur in the aged ECM, that make it less receptive to innervation. However, they also indicate that, along with the ECM, factors produced by the cellular components of the blood vessel wall are essential, at least for the maintenance of the sympathetic innervation.

Aging↗

[Resection of pelvic retroperitoneal neoplasm and reconstruction of iliac blood vessels: report of 22 cases].

OBJECTIVE: To study the surgical manipulation of iliac blood vessels invaded by pelvic tumors in order to raise the resection rate. METHODS: We reviewed 22 cases of resection for pelvic retroperitoneal tumors along with the reconstruction of iliac blood vessels in our hospital from July 1994 to January 2000. In 22 cases, 8 received operation on the right iliac arteries and veins, and 14 on the left. RESULTS: Follow-up for 4 months to 5 years and 10 months (average 3.6 years) showed that 3 patients had recurrence and needed secondary operation. All the grafts were patent except one vein graft occlusion 7 months after operation. CONCLUSION: Resection of pelvic retroperitoneal neoplasm combined with reconstruction of iliac blood vessels is safe, effective and practical to raise the excision rate and decrease the recurrence rate.

Adult↗

reg6 is required for branching morphogenesis during blood vessel regeneration in zebrafish caudal fins.

Postnatal neovascularization is essential for wound healing, cancer progression, and many other physiological functions. However, its genetic mechanism is largely unknown. In this report, we study neovascularization in regenerating adult zebrafish fins using transgenic fish that express EGFP in blood vessel endothelial cells. We first describe the morphogenesis of regenerating vessels in wild-type animals and then the phenotypic analysis of a genetic mutation that disrupts blood vessel regeneration. In wild-type zebrafish caudal fins, amputated blood vessels heal their ends by 24 h postamputation (hpa) and then reconnect arteries and veins via anastomosis, to resume blood flow at wound sites by 48 hpa. The truncated vessels regenerate by first growing excess vessels to form unstructured plexuses, resembling the primary capillary plexuses formed during embryonic vasculogenesis. Interestingly, this mode of vessel growth switches by 8 days postamputation (dpa) to growth without a plexus intermediate. During blood vessel regeneration, vessel remodeling begins during early plexus formation and continues until the original vasculature pattern is reestablished at approximately 35 dpa. Temperature-sensitive mutants for reg6 have profound defects in blood vessel regeneration. At the restrictive temperature, reg6 regenerating blood vessels first fail to make reconnections between severed arteries and veins, and then form enlarged vascular sinuses rather than branched vascular plexuses. Reciprocal temperature-shift experiments show that reg6 function is required throughout plexus formation, but not during later growth. Our results suggest that the reg6 mutation causes defects in branch formation and/or angiogenic sprouting.

Animals↗

Relationships between beta-amyloid (A beta) deposits and blood vessels in patients with sporadic and familial Alzheimer's disease.

The density of diffuse, primitive and classic beta-amyloid (A beta) deposits was studied in relation to the incidence of blood vessels in the superior frontal gyrus of nine cases of sporadic Alzheimer's disease (SAD), two cases of familial Alzheimer's disease (FAD) with amyloid precursor protein (APP) mutations (APP717, Val --> Ile), and eight cases of FAD not linked to chromosomes 21, 14 or 1. Stepwise multiple regression was used to determine for each patient whether variations in the density of A beta deposits along the cortex were significantly correlated with the incidence of blood vessels. In the majority of FAD and SAD cases, the density of the diffuse and primitive type A beta deposits was not related to blood vessels. However, the incidence of the larger diameter (> 10 microns) blood vessels was positively correlated with the density of the classic A beta deposits in eight (89%) SAD and two (20%) FAD cases. The data suggest that the densities of vessels and deposits were not significantly correlated between cases but only within cases, suggesting a strictly local effect. In addition, the spatial association between classic A beta deposits and blood vessels may be more apparent in SAD compared with FAD cases.

Aged↗

Hemostasis of punctured blood vessels using high-intensity focused ultrasound.

The hemorrhagic complications of vascular injury can be significant. We report on the use of high-intensity focused ultrasound (HIFU) to stop the hemorrhage of punctured blood vessels in pigs. Two HIFU transducers with frequencies of 3.5 and 2.0 MHz, each equipped with a water-filled conical housing, were used. Major blood vessels (femoral artery and vein, axillary artery, carotid artery and jugular vein), 2-10 mm in diameter, of anesthetized pigs were exposed surgically and punctured with 14- and 18-gauge needles to produce moderate to profuse bleeding. Complete hemostasis was achieved in less than 3 min of HIFU treatment in most blood vessels, and all vessels were patent after the treatment. Both HIFU frequencies were effective in producing hemostasis. Gross examination of the HIFU-treated vessels showed a consistent hardening of the soft tissue surrounding the blood vessels, providing a seal for the puncture hole. Microscopic examination of the vessels showed a remarkably localized HIFU treatment, resulting in coagulation of the adventitia, and an extensive fibrin network around the vessels and in the puncture hole. The vessel walls exhibited focal swelling, without evidence of irreversible injury. HIFU may provide a useful method for achieving hemostasis of punctured and traumatized blood vessels in a variety of clinical settings.

Animals↗

[The architecture of the cutaneous blood vessels in scent pigs].

OBJECTIVE: To study the anatomy of cutaneous blood vessels of the scent pig, and to provide an animal model for research in plastic surgery. METHODS: Seven Chinese mini-pigs (scent pigs) were used in the study. RESULTS: 1. The scent pig is small, easy to house, rich in panniculus adiposus. 2. The origin of cutaneous blood vessels is divided into three types: the musculo-cutaneous perforator, the intermuscular septal perforator and the direct cutaneous vessel. There are some differences in distribution, size, and architecture from the characteristics of that of human being. 3. The architecture of cutaneous vessels could be divided into four vascular plexuses: the profound vascular plexus, middle vascular plexus, superficial vascular plexus of the superficial fascia and the subdermal vascular plexus. 4. The density of vessels and vessel plexuses in the neck and trunk is higher than that of the legs. CONCLUSION: In terms of the morphology of cutaneous blood vessels, the scent pig is an ideal animal model for skin flap study.

Animals↗