Ultrastructural and morphometric aspects of ageing in the retinal capillaries of rats

Age-related morphological, ultrastructural and morphometric changes in the capillaries of the superficial and deep plexuses of the rat retina were studied in animals aged from 3 to 15 months. Our results suggest that age-related morphological alterations start occurring in the retina of rats at about 12 months of age. Increased glycogen deposits, pinocytotic vesicles, residual bodies and cell debris were observed in both the endothelial and pericytic cells of 12- and 15-month-old animals. In addition, heterogeneous osmiophilic accumulations, electron-transparent spaces were observed in the basement membrane as well as projections of the basement membrane towards the neighboring cells. Morphometric examination of the two vascular plexuses studied did not show differences in the area of the endothelial or pericytic cells, basement membrane or vascular lumen between rats of different ages.

Atherosclerosis morphology and pathogenesis

Atherosclerosis is a very common and important disease being the most important cause of mortality in Brazil. Indeed, in 1995, 23.3% of deaths, all ages, in our country, were the consequence of atherosclerosis. This percentage grows to 26.3% for S. Paulo and 32.7% for Rio Grande do Sul. Morphologically, there are 3 main types of lesions: fatty streaks, fibrous plaques, and complicated lesions. Fatty streaks are inocuous and occur early in life. In some persons, with age, they change into fibrous plaques that may lead to stenosis. They also may become complicated by erosion, calcification, hemorrhage and thrombosis. Atherosclerosis is initiated by endothelial functional alterations responsible for increase in permeability to macromolecules, adhesion, and migration of monocytes-macrophages and lymphocytes plus recruitment of platelets and smooth-muscle medial cells. Adhesion molecules, cytokines, growth factors, and free radicals are locally synthesized, favoring proliferation of extracellular matrix and progression of the lesion. Experimental, clinical, and epidemiological evidence point to the importance of lipids, mainly cholesterol-rich low-density lipoprotein (LDL), as one of the most important molecules involved in the genesis and progression of atherosclerosis. Patients with a genetic disorder of cholesterol metabolism (familial hyperlipidemia), caused by a decrease in the availability of receptors for LDL, develop severe atherosclerosis early in life. A series of other factors, such as age, diabetes melitus, diet, hypertension, lack of exercise, elevated hemocysteinemia, immunological disorders, and coagulation instability, are related to the progression of atherosclerosis. All of them are capable of altering the endothelium or increasing the offer of LDL. All the above-mentioned factors are systemic; but atherosclerosic lesions are focal, located at preferential sites such as the emergence of colaterals, bifurcations, and curvatures of arteries, all areas in which the laminar flow is disturbed. In these areas shear stress is diminished favoring the prolongation of permanence time of lipid particles, cells, cytokines, growth factors, etc., in the vicinity of the endothelium. Moreover, the endothelium has sensors that act as transducers of mechanical forces in biological responses. Experimental data demonstrate that the number and quality of adhesion molecules, cytokines, and growth factors synthetized, as well as the local production of radicals, and pro and anticoagulation factors may change with shear stress favoring or not the local establishment and progression of atherosclerotic lesions.

Architecture of the caudal vena cava wall of the dog at the level of the liver caudate lobe

The vascular segment of the caudal vena cava of the dog at the level of the caudate lobe was shown to be intimately related to hepatic tissue through the hepatic capsule and parenchyma. The tunica adventitia of the caudal vena cava was formed mainly by smooth muscle cells with collagen and elastic fibers arranged in bundles. The thin tunica media of the vein was also formed by smooth muscle cells, collagen and elastic fibers arranged in bundles. The tunica intima presented an elastic sub-endothelial network. The hepatic segment of the caudal vena cava showed a myoconnective architecture and propulsive characteristics in terms of its hemodynamic pattern.

Static lung compliance and body pressures in Tupinambis merianae with and without post-hepatic septum

The surgical removal of the post-hepatic septum (PHS) in the tegu lizard, Tupinambis merianae, significantly reduces resting lung volume (VLr) and maximal lung volume (VLm) when compared with tegus with intact PHS. Standardised for body mass (MB), static lung compliance was significantly less in tegus without PHS. Pleural and abdominal pressures followed, like ventilation, a biphasic pattern. In general, pressures increased during expiration and decreased during inspiration. However, during expiration pressure changes showed a marked intra- and interindividual variation. The removal of the PHS resulted in a lower cranio-caudal intracoelomic pressure differential, but had no effect on the general pattern of pressure changes accompanying ventilation. These results show that a perforated PHS that lacks striated muscle has significant influence on static breathing mechanics in Tupinambis and by analogy provides valuable insight into similar processes that led to the evolution of the mammalian diaphragm. © 2003 Elsevier Science B.V. All rights reserved.

Características estruturais da parede das artérias renal e femoral de coelho (Oryctolagus cuniculus)

In the renal and femoral arteries of rabbit was verified that both vessels had walls structured by myostromal components, despite of their different distributive of blood, being the renal artery a visceral blood vessel and the femoral artery a parietal vessel. This wall pattern in these vessels concerned to presence of connective stromal elements (collagen and elastic fibres and lamellae) and smooth muscle cells coexisting with some equilibrium in the wall structure of the renal and femoral arteries, mainly in the medial layer architecture. An intimal folding pattern was verified around the vascular lumen, possibly related to capacitance of the both arteries regarding to variability of pressure levels in cardiac cycle. Furthermore, myostromal relations of connective elements and smooth muscle cells verified in the medial layer and the network formed by connective elements in the adventitial layer of these arteries contributed to maintenance of wall viscoelasticity properties of the vessels.

Morphology of oesophagus and crop of the partrigde Rhynchotus rufescens (Tiramidae)

Twenty adult partridges Rhynchotus rufescens were used to study the morphology of oesophagus and crop. Materials to the morphologic study were collected and lengths of the oesophagus and of the crop were measured. For histological study, fragments of the oesophagus and of the crop were stained routinely with Masson's trichrome stain. Total oesophagus was larger in females. In the entrance of the thorax, its ventral wall is enlarged broadly, forming the crop, which is larger in males. Oesophagus mucosa is constituted by stratified squamous epithelium, with mucous glands and lymphatic tissues. There are three layers of smooth muscle, involved in serosa. The histological structure of the crop is similar to the oesophagus. The mucous glands are reduced in size and the lymphatic tissues are dispersed in the connective tissue. There is a thin stratum of smooth muscle and other two wider layers of longitudinal and circular musculature.

Molecular hybridization: A useful tool in the design of new drug prototypes

Molecular hybridization is a new concept in drug design and development based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hyrid compound with improved affinity and efficacy, when compared to the parent drugs. Additionally, this strategy can results in compounds presenting modified selectivity profile, different and/or dual modes of action and reduced undesired side effects. So, in this described several example of different strategies for drug design, discovery and pharmacomodulation focused on new innovative hybrid compounds presenting analgesic, anti-inflammatory, platelet anti-aggregating, anti-infections, anticancer, cardio- and neuroactive properties.

Características ultraestruturais do segmento abdominal da aorta de rato albino

The objective of the present research was to investigate the ultrastructural peculiarities of the aortic wall of the rat. Seven young adult rats were used, from which fragments of the infrarenal abdominal aorta were collected. After collection, the vascular segments were fixed and sent for analysis by scanning electron microscope. The elastic lamellae appear interposed with smooth muscular fibers; this pattern was verified mainly at the medial layer structure. Among the mural elements a well defined interrelationship was established through connective lamellae of the arterial wall. The collagen lamellae mainly provided anchoring among the elastic and smooth muscular constituents. The intimal layer showed special ultrastructural features, such as a non-continuous inner elastic lamina presented in certain sites of the vascular wall, followed by endothelial pores. This mural pattern of the abdominal aorta provided support to vascular functions such as shrinkage among the laminar composition of the arterial layers, also acting in mechanical properties of the vascular wall, such as viscoelasticity and contractility - essential actions to blood vessel hemodynamics.

Doxazosin reduces cell proliferation and increases collagen fibers in rat prostatic lobes

We investigated the effects of doxazosin (Dox), an alpha-adrenoceptor antagonist used clinically for the treatment of benign prostatic hyperplasia (BPH), on the rat prostatic complex by assessing structural parameters, collagen fiber content, cell proliferation, and apoptosis. Adult Wistar rats were treated with Dox (25 mg/kg per day), and the ventral (VP), dorsolateral, and anterior prostate (AP) regions of the prostate complex were excised at 3, 7, and 30 days after treatment. At 24 h before being killed, the rats were injected once with 5-bromodeoxyuridine (BrdU; thymidine analog) to label mitotically active cells. The prostates were weighed and processed for histochemistry, morphometry-stereology, immunohistochemistry for BrdU, Western blotting for proliferating cell nuclear antigen (PCNA), and the TUNEL reaction for apoptosis. Dox-treated prostate lobes at day 3 presented increased weight, an enlarged ductal lumen, low cubical epithelial cells, reduced epithelial folds, and stretched smooth muscle cells. However, at day 30, the prostates exhibited a weight reduction of ∼20% and an increased area of collagen and reticular fibers in the stromal space. Dox also reduced epithelial cell proliferation and increased apoptosis in the three prostatic lobes. Western blotting for PCNA confirmed the reduction of cell proliferation by Dox, with the AP and VP being more affected than the dorsal prostate. Thus, Dox treatment alters epithelial cell behavior and prostatic tissue mechanical demand, inducing tissue remodeling in which collagen fibers assume a major role. © 2007 Springer-Verlag.

Exercise training improves relaxation response and SOD-1 expression in aortic and mesenteric rings from high caloric diet-fed rats

Background. Obesity has been associated with a variety of disease such as type II diabetes mellitus, arterial hypertension and atherosclerosis. Evidences have shown that exercise training promotes beneficial effects on these disorders, but the underlying mechanisms are not fully understood. The aim of this study was to investigate whether physical preconditioning prevents the deleterious effect of high caloric diet in vascular reactivity of rat aortic and mesenteric rings. Methods. Male Wistar rats were divided into sedentary (SD); trained (TR); sedentary diet (SDD) and trained diet (TRD) groups. Run training (RT) was performed in sessions of 60 min, 5 days/week for 12 weeks (70-80% VO2max). Triglycerides, glucose, insulin and nitrite/nitrate concentrations (NOx -) were measured. Concentration- response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained. Expression of Cu/Zn superoxide dismutase (SOD-1) was assessed by Western blotting. Results. High caloric diet increased triglycerides concentration (SDD: 216 ± 25 mg/dl) and exercise training restored to the baseline value (TRD: 89 ± 9 mg/dl). Physical preconditioning significantly reduced insulin levels in both groups (TR: 0.54 ± 0.1 and TRD: 1.24 ± 0.3 ng/ml) as compared to sedentary animals (SD: 0.87 ± 0.1 and SDD: 2.57 ± 0.3 ng/ml). On the other hand, glucose concentration was slightly increased by high caloric diet, and RT did not modify this parameter (SD: 126 ± 6; TR: 140 ± 8; SDD: 156 ± 8 and TRD 153 ± 9 mg/dl). Neither high caloric diet nor RT modified NO x - levels (SD: 27 ± 4; TR: 28 ± 6; SDD: 27 ± 3 and TRD: 30 ± 2 μM). Functional assays showed that high caloric diet impaired the relaxing response to ACh in mesenteric (about 13%), but not in aortic rings. RT improved the relaxing responses to ACh either in aortic (28%, for TR and 16%, to TRD groups) or mesenteric rings (10%, for TR and 17%, to TRD groups) that was accompanied by up-regulation of SOD-1 expression and reduction in triglycerides levels. Conclusion. The improvement in endothelial function by physical preconditioning in mesenteric and aortic arteries from high caloric fed-rats was directly related to an increase in NO bioavailability to the smooth muscle mostly due to SOD-1 up regulation. © 2008 de Moraes et al; licensee BioMed Central Ltd.

The possible involvement of hyperpolarizing mechanisms in histamine-induced relaxation of the rat portal vein

The present study evaluated the effects of histamine 10 -2 M on longitudinal preparations of rat portal vein. It was observed that histamine 10 -2 M induced relaxation of rat portal vein preparations pre-contracted with phenylephrine 10 -4 M. On the other hand, no pharmacological effects were observed in preparations not pre-contracted. The observed histamine-induced relaxing effect was absent in preparations pre-contracted with KCl (120 mM) or in the presence of depolarizing nutritive solution. However, the histamine-induced relaxation was still present in the endothelium-removed preparations. The histamine-induced relaxation also was not prevented by astemizole (10 -6 M, 10 -5 M and 10 -4 M), cimetidine (10 -5 M, 10 -4 M and 10 -3 M) or thioperamide (10 -6 M, 10 -5 M and 10 -4 M), selective antagonists H 1, H 2 and H 3, respectively. The presence of L-NAME 10 -4 M or L-NAME 10 -4 M plus indomethacin 10 -5 M also did not prevent the histamine-induced relaxation observed in rat portal vein. Thus, the histamine-induced relaxation observed in rat portal vein appears to involve a non-endothelial hyperpolarizing mechanism independent of H 1, H 2 and H 3 receptors.

Plasma lipid profile of experimentally induced hyperlipidemic New Zealand white rabbits is not affected by resveratrol

Hyperlipidemia is well recognized as an important risk factor in the development of atherosclerosis. Low-density lipoproteins (LDL) are components of cholesterol that are highly associated to an increased risk of cardiovascular diseases. Hypercholesterolemia induces proteolytic and oxidative changes in vasculature, leading to a local inflammatory response. Since dietary antioxidants have attracted considerable attention as preventive and therapeutic agents, the polyphenolic compound resveratrol seems to play an important role in prevention of human atherosclerosis. Researches show that resveratrol inhibits LDL oxidation and platelet aggregation, as well as vascular prolifer ation of smooth muscle cells. However, recent findings in animal models reveal conflicting results regarding its effects on plasma lipid levels. The aim of the present study was to evaluate the effect of resveratrol on plasma biochemistry profile in New Zealand white rabbits submitted to a hypercholesterolemic diet. Twenty healthy, male, adult New Zealand white rabbits were fed with ordinary diet for one week before being divided into four treatment groups, containing five animals each. Group CT received maintenance diet; group R received maintenance diet and resveratrol (3mg/kg/day) given orally; group CL received maintenance diet enriched with 1.5% cholesterol; and group CR received maintenance diet enriched with 1.5% cholesterol and resveratrol (3mg/kg/day) given orally. During the experiment, from each animal, samples of 3mL venous blood were collected in heparin twice monthly for measurements of total cholesterol, triglycerides, and low- and high-density lipoproteins. The data analysis revealed that resveratrol did not have a hypolipidemic effect in experimentally induced hypercholesterolemic New Zealand white rabbits.

Arquitetura da parede vascular de segmentos torácico e abdominais da aorta de macaco prego (Cebus apella)

The intimal layer of the thoracic and abdominal aortic segments of Cebus apella monkey presented an evident inner elastic lamina. The medial layer of the thoracic aorta segment showed a basic lamellar elastic pattern having a medium average of 23.12 lamellae per analyzed cut sections, which appeared disposed circular and oblique relatively to the aortic lumen. The aortic adventitial layer, at this level, was formed mainly by collagen fibers, irregularly disposed between elastic fibers and smooth muscle cells. The aortic abdominal portion, in this monkey, at the suprarenal level presented a medium number of 19.12 elastic lamellae which showed a relatively disorganized and broken up pattern. At the infrarenal level the aortic medium layer showed a medium average of 11.75 elastic lamellae and next to the emission of the internal iliac arteries it was found only a middle average of 8.37 elastic lamellae intermingled with smooth muscle cells and collagen fibers whose concentration seemed to be increased next to the adventitial layer. The external elastic lamina was only present in the more distal aortic segment near to the emission of the internal iliac arteries.

Exercise training ameliorates the impairment of endothelial and nitrergic corpus cavernosum responses in diabetic rats

Aims: The effect of exercise training (ET) on vascular responsiveness in diabetes mellitus has been largely well studied. However, limited studies have investigated the effects of ET on functional responses of the corpus cavernosum (CC) in diabetic animals. Therefore, the aim of this study was to investigate whether prior ET prevents the impairment of erectile function in streptozotocin-induced diabetic rats. Main methods: Rats were exercised for four weeks prior to the induction of diabetes, and then again for another 4 weeks thereafter. Concentration-response curves to acetylcholine, sodium nitroprusside, Y-27632, BAY 412272 and phenylephrine (PE) were obtained in CC. The excitatory and inhibitory effects of electrical-field stimulation were also evaluated. Key findings: Plasma SOD levels were markedly decreased in the sedentary diabetic group (D-SD) as compared to control sedentary animals (C-SD), approximately 53% (P < 0.05) and this reduction was restored in trained diabetic animals. Physical training restored the impairment of endothelium-dependent and -independent relaxation responses seen in the D-SD group. The potency values for Y-27632 in the CC were significantly reduced in the D-SD group, which was reversed by physical training. The impairment of electrical-field stimulation (EFS)-induced relaxation seen in the D-SD group was restored by physical training. On the other hand, both EFS-induced contractions and concentration-response curves to PE in cavernosal strips were not modified by either diabetes or physical training. Significance: Practice of regular physical exercise may be an important approach in preventing erectile dysfunction associated with diabetes mellitus by re-establishment of the balance between NO production and its inactivation. © 2010 Elsevier Inc. All rights reserved.

Prostatic stromal cells of old gerbils respond to steroidal blockades creating a microenvironment similar to reactive stroma

The present study examined the changes in prostatic stroma of old gerbils (18 months) submitted to orchiectomy associated or not with steroidal blockades. Animals were divided into six groups, all surgically castrated except the control group composed of intact animals. The other two controls were formed by castrated animals, one that received and one that did not receive the drug vehicle. In the experimental groups, doses of flutamide (10 mg/kg/day) and/or tamoxifen (1 mg/kg/48 h) were applied for 1, 3, 7 and 30 days post-castration. The methodologies involved were: morphological (HE, Gömöri reticulin, Picrosirius-hematoxylin), immunohistochemical (tenascin, type IV collagen) and ultrastructural analyses. Gradually, the epithelial compartment was significantly exceeded in volume by the stromal compartment, characterizing regression but not atrophy of the gland. The smooth muscle cell frequency increased significantly after 30 days and participated effectively in the stromal increase. Large collagen I and tenascin deposits in the subepithelial region were a hallmark of prostatic acini in the experimental groups up to 7 days, while in the 30-day group these elements practically disappear. Fibroblasts with reactive aspect, changes in basement membrane structure and maintenance and/or increase of blood vessels were also associated with treatments. These results showed, in part, the sensitivity of stromal components to suppressed hormones and favored the creation of a differentiated glandular microenvironment. Therefore, the data suggest the importance of considering aging when analyzing aspects of prostatic regression between rodents and humans after hormonal ablation. © 2011 Elsevier Masson SAS. All rights reserved.