Interaction between angiotensin II receptors and alpha-adrenoceptors in the murine vascular system

The mouse major conductive (aorta and carotid and superior mesenteric arteries) and small resistance arteries (first branch mesenteric artery) have a multiple population of adrenoceptor (ARs) and angiotensin II (Ang II) receptors capable of initiating contraction or relaxation. This thesis uses pharmacological methods to describe responses mediated by these receptors and to explore interactions between them. On mouse aorta Ang II had a dual effect that could be best observed in the presence of elevated tone (by 5HT), initially causing contraction at lower concentrations, followed by a slow relaxant effect that became dominant over time or at higher concentrations. The contraction was attenuated by Losartan and the relaxation by PD123319 (AT1 and AT2 antagonists, respectively) indicating physiologically opposing actions of AT1 and AT2 receptors. The relaxation was abolished by L-NAME or endothelium removal, revealing a larger contraction to Ang II. This indicates an AT1 action to contract vascular smooth muscle directly and an AT2 action on endothelium to release nitric oxide. The potential influence of Ang II on the effects of noradrenaline was studied. First the interaction of the relaxant (endothelial) effects of the two agents was explored by testing the effect of a "relaxant" concentration of Ang II (30nM) against the effects of UK14304, an alpha2-AR agonist, serving as a surrogate for noradrenaline in order to avoid activation of other adrenoceptors. This revealed no synergism or other significant interaction, which contrasted with a strong interaction between Ang II and the contractile effects of alpha2-AR activation in other blood vessels. Ang II was then tested against the contractile effects of noradrenahne, applied as a cumulative concentration response curve. Preincubation with Ang II (30nM) significantly reduced the contractile response to NA (p<0.0001); this effect was enhanced by losartan and blocked by PD123319. Thus the major influence of Ang II upon noradrenaline's actions is an AT2-mediated attenuation that becomes greater if AT1 receptors are blocked. In both carotid and superior (main) mesenteric arteries the contractile effect of Ang II was dominant. In first branch mesenteric arteries the main effect of angiotensin II was relaxation; this was reversed to contraction by L-NAME suggesting that it was of endothelial origin. The balance of smooth muscle contractile (AT1) and endothelial relaxant (AT2) -mediated responses, thus varies amongst arteries. A fluorescent derivative of Ang II, Rhodamine-Angiotensin II-Human (Rho-Ang II-H), was used to visualise angiotensin receptors on dissociated arterial cells and intact vessels, employing confocal microscopy. Losartan and PD123319 were used as competitor ligands to identify the receptor subtypes that were labelled by the fluorescent compound. This provided evidence for the presence of both AT receptor subtypes on both smooth muscle and endothelial cells. This was accomplished on both aorta and main (superior) mesenteric arteries. In conclusion, mouse arterial endothelium has AT2 that promote the release of nitric oxide, detectable as smooth muscle relaxation and vascular smooth muscle has contractile AT1. This shows that the previously demonstrated dual, opposing actions of angiotensin II are due to receptors situated on different cell types. There was also, however, evidence for the presence of both receptor types on both smooth muscle and endothelial cells. (Abstract shortened by ProQuest.)

Effects of L-Carnitine on the sperm parameters disorders, apoptosis of spermatogenic cells and testis histopathology in diabetic Rats

Background: Diabetes mellitus affects male reproductive system that is known to cause male infertility. Objective: The aim of the present study was to assess the effects of L-carnitine (LC) on sperm parameters, apoptosis of spermatogenic cells and testis histopathology in Streptozotocin-induced diabetic Rats. Materials and Methods: The study was carried out on 36 male Wistar adult rats (220 ± 30 gr) randomly divided into six groups (n = 6/each). 1 (Control); 2 (LC 100 mg/kg); 3 (Diabetic); 4, 5, and 6 (Diabetic + LC 50 or 100 or 200 mg/kg, respectively). Daily injections were administered intraperitoneally for 48 days. Then, rats were sacrificed, left testis and epididymis were harvested for sperm analysis and histopathology, morphometric and spermatogenesis assessments, and Tunnel assay. Results: L-carnitine in group 6 significantly decreased blood glucose level (p &lt; 0.01) in comparison with group 3. L-carnitine in groups 5 and 6 significantly (p &lt; 0.001) and dose-dependently increased the count, motility, viability, maturity, and chromatin quality of sperm and decreased the abnormal morphology of sperm in comparison with group 3. In groups 4, 5, and particularly 6, in comparison with group 3, there has been a significant difference in the increase of seminiferous tubule diameter, germinal epithelium height (p &lt; 0.001), maturity quality of the seminiferous tubules (p &lt; 0.001), decrease apoptosis of spermatogenic cells (p &lt; 0.001), and testis tissue histopathological complications. Conclusion: The data obtained from the present study suggest that in the diabetic rats, LC decreases serum glucose level, improves the diameter and thickness of the epithelium of spermatogenic cells, reduces germ cells’ apoptosis, and improves epididymal sperm parameters. Therefore, it seems that LC plays an effective role in diabetes-induced infertility

Interaction between angiotensin II receptors and α-adrenoceptors in the murine vascular system

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Endothelial Vasodilator Angiotensin Receptors are Changing in Mice with Ageing

Background: The vascular function of Angiotensin II-type-2 receptors in adults is controversial. We sought their location and function in mouse aortic rings at young and old mice. Materials and Methods: Male C57Bl mice (aged 4 and 14 months) were killed by CO2. The descending thoracic aorta was cleaned and dissected into rings. Aortic rings were mounted in Krebs’ solution at 37 °C and then setup in a multi-myograph. Also segments of aorta were incubated with or without antagonists then TMR-Angiotensin II and/or QAPB were added. Results: At 4 months, angiotensin II, at low concentrations, caused losartan-sensitive contraction higher concentrations (100nmol/L) caused relaxation sensitive to endothelial denudation, L-NAME or PD123319. Angiotensin II-type-1 receptors blockade plus L-NAME revealed PD123319-sensitive contraction. At old mice, aortic relaxation to angiotensin II was lost. At young mice, Losartan and PD123319, together but not separately, abolished binding of fluorescent TMR-angiotensin II, to endothelium and smooth muscle, indicatin Angiotensin II-type-1 and Angiotensin II-type-2 receptors in both cell types. In contrast, at 14 months endothelial fluorescence was eliminated by losartan. Conclusion: Aortic endothelium of young adult mice has Angiotensin II-type-2 receptors that release vasodilator nitric oxide. This is lost in old age, explaining age-related loss of vasodilatation by Angiotensin II. Aortic smooth muscle has pro-contractile Angiotensin II-type-1 and Angiotensin II-type-2 receptors in young and old mice. Reciprocal actions of angiotensin II are, due to Angiotensin II-type-1 and Angiotensin II-type-2 receptors situated on different cell types but only at young ages, Angiotensin II-type-1 receptors of unknown function are present on endothelium

Geology, mineralogy and geochemistry of Ferezneh ferromanganese anomaly, east of Sangan mines complex, NE Iran

Introduction The Ferezneh prospect area is one of the eastern anomalies of Khaf’s Sangan iron mine. The Sangan mines complex is located within the Khaf-Kashmar-Bardeskan volcano-plutonic and metallogenic belt in northeastern Iran. The Sangan mine is the largest Fe skarn in western Asia, having a proven reserve of over 1000 Mt iron ore @ 53% Fe (Golmohammadi et al., 2015) and consisting of three parts; western, central and eastern Sangan, each part including several anomalies. In this study, Ferezneh (North and West) prospect area which is an eastern anomaly of the Sangan iron ore is discussed. Ferezneh anomaly is located in 60°36'7" - 60°34'27"E and 34°30'47" - 34°29'46"N, 35 km south of the city of Taybad, 10 km southeast of Karat and 1.5 km southwest of Ferezneh village. The purpose of this study was to prepare a geologic map for separation and identification of the intrusions, determining their relationships with mineralization, distinguishing the type of mineralization, mineralogy, petrology and geochemistry of the mineral deposits, and finally their relationship with other major Sangan’s deposits. Materials and methods In order to achieve the objectives of the study: 1- 140 thin sections of the intrusive rocks, marble limestone and dolomite, as well as 40 polished sections of ore were taken in an area of 9.5 km2. Mineralogy and mineralization studies were performed in the Economic Geology Laboratory of Ferdowsi University of Mashhad. 2- A few samples were selected for X-ray diffraction analysis in order to ensure accuracy of mineralogical studies and were sent to Binalood Laboratory in Tehran. 3- In addition to major and minor elements geochemistry study of the ores, 10 samples were sent to East Amitis Laboratory in Mashhad for XRF analysis and also to Canada S.G.S Laboratory for ICP-MS analysis. Discussion and results Mineralization in the Ferezneh prospect area was limited to iron and manganese oxides in the form of massive and stratabound in recrystallized limestone that followed the structure pattern. Iron oxides often include goethite and hematite; while manganese oxides are pyrolusite, psilomelane and lesser amounts of cryptomelane. Small spots of rutile are rarely seen. The gangue minerals are dolomite, calcite and cryptocrystalline quartz. XRD analysis shows that iron and manganese oxides are the only metallic minerals. The geochemistry of mineralization was studied by ICP-MS and XRF analysis for major oxides, trace elements and REE. The range of Fe anomaly changes from 43.5 to 68% and Mn anomalies vary between 1.9 and 4.8 %. The range of Cu varies from 20 to 1063 ppm and the range of As differs between 20 and 1269 ppm, no Cu and As mineralization has been observed. Mn and Fe oxides uptake trace elements. In the Fe:Mn:Si ternary diagram, ten of the analyzed samples were plotted in the characteristic compositional field for Fe-rich hydrothermal. In the Fe:Mn:(Co+Ni+Cu)×10 ternary diagram, data were also plotted in hydrothermal fields. Minor and trace elements in the binary diagram of Ni+Co vs. Cu+Zn+Pb+Mo+V+As (Crerar et al., 1982) show samples within the field for hydrothermal deposits. REE pattern shows positive Eu anomaly and the Eu/Eu* ratio changes from 2 to 7, LREE/HREE ratio varies between 2.25 and 13.78, the mean being 6.94. Rare earth element contents show relatively low to moderate subtraction pattern. LREE have more variations than HREE values that have been fixed. Enrichment of LREE over HREE and positive Eu anomaly, are the key indications of hydrothermal origin for the ore deposits and low amounts of REE are the characteristic for hydrothermal deposits (Xu Bao et al., 2008). As, Cu, Pb, Zn and Sb act as trace indicator elements in reaching the hidden epithermal or hydrothermal sulfide deposit in depth. Although the type of mineralization in the main parts of Sangan is skarn (Karimpour and Malekzadeh Shafaroudi, 2006; Karimpour and Malekzadeh Shafaroudi, 2008; Golmohammadi et al., 2015), there is no evidence of limestone skarnification, skarn minerals and magnetite mineralization in the Ferezneh prospect area. Based on the listed data and interpretations, there is no relationship and similarity between Sangan mineralization and Ferezneh ferromanganese anomaly. This anomaly may be related to a younger mineralization and might be associated with the function of supersion fluid by leaching the sulfide hydrothermal deposits that form in the fault zones. References Crerar, D.A., Namson, J., Chyi, M.S., Williams, L. and Feigenson, M.D., 1982. Manganiferous cherts of the Franciscan Assemblage: I. General geology, ancient and modern analogues and implications for hydrothermal convection at oceanic spreading centers. Economic Geology, 77(3): 519-540. Golmohammadi, A., Karimpour, M.H., Malekzadeh Shafaroudi, A. and Mazaheri S.A., 2015. Alteration-mineralization, and radiometric ages of the source pluton at the Sangan iron skarn deposit, northeastern Iran. Ore Geology Reviews, 65(2): 545-563. Karimpour, M.H. and Malekzadeh Shafaroudi, A., 2006. Comparison of the geochemistry of source rocks at Tannurjeh Au-bearing magnetite and Sangan Au-free magnetite deposits, Khorasan Razavi, Iran. Iranian Journal of Crystallography and Mineralogy, 13(1): 3–26. (in Persian with English abstract) Karimpour, M.H. and Malekzadeh Shafaroudi, A., 2008. Skarn geochemistry – mineralogy and petrology of source rock, Sangan iron mine, Khorasan Razavi, Iran. Scientific Quarterly Journal of Geosciences, 17(65), 108–125. (in Persian with English abstract) Xu Bao, S., Yang Zhou, H., Tong Peng, X., Wu Ji, F. and Qiang Yao, H., 2008. Geochemistry of REE and yttrium in hydrothermal fluids from the Endeavour segment. Juande Fuca Ridge. Geochemical Journal, 42(4): 359–370. <br

Combined protective effect of zinc oxide nanoparticles and melatonin on cyclophosphamide-induced toxicity in testicular histology and sperm parameters in adult Wistar rats

Background: Cyclophosphamide (CP) has been known as an anticancer drug with several side effects on various organs such as a male reproductive system that can cause infertility. Objective: To evaluate the possible combined effects of zinc oxide nanoparticles (nZno) and melatonin (Mel) on sperm parameters and histopathological changes of the testis in CP-treated rats. Materials and Methods: 42 adult male Wistar rats were divided into six groups. GI: control, GII: 60 mg/kg/wk CP, GIII and GIV, 10 mg/kg/wk Mel and 5mg/kg/wk nZno and GV: 5 mg/kg/wk nZno and 10 mg/kg/wk Mel were given 2 hr prior to CP injection, respectively,GVI: 5mg/kg/wk nZno and 10 mg/kg/wk Mel simultaneously. After 8 wk of treatment, rats were sacrificed and testis and epididymis were harvested for further evaluation. Results: The CP-treated group showed significant decreases in the body, testes and epididymis weights and sperm parameters (sperm count, viability, motility) with an increase abnormal sperms when compared with the control (p<0.001), as well as many histological alterations included decreased diameters of seminiferous tubules and Johnsen&rsquo;s Testicular Score (with degeneration, desquamation, multi-nucleated giant cell formation), whereas combined treatment (GV), showed more protective effects on CP-induced reproductive system damage compared with groups III or IV (p<0.001). Conclusion: These results suggest simultaneous administration of Mel and nZno have more effectively protections against CP-induced reproductive damage than Mel or nZno alone

Study of relation between Neck Shaft Angle (NSA) and mineral density of the femoral head among old post menopausal women in east part of mazandaran province

Background: Diversity in Proximal Femur Geometric Parameters (PFGPs) will be led to frequency changes in hip fractures. The purpose of the present study is to investigate of the relation between Bone Mineral Density (BMD) in proximal femur with Neck Shaft Angle (NSA) in both of osteoporotic and normal groups among old postmenopausal women in eastern part of Mazandaran province as a appropriate indicator to predict hip fractures occurance. Materials and Methods: Among 5103 postmenopausal women reffered to bone densitometry center, for 221 postmenopausal women who had inclusion criteria to this study, simultaneously by using densitometry system and completing a standard questionnaire, history of disease and demographic information including body mass index (BMI) were recorded for each patient. Obtained information from densitometers was analyzed by the statistical software SPSS version 16 and Pearson correlation coefficient test was used. Results: Geometric parameters of 221 post-menopausal women aged 50 to 60 were analyzed. The mean of neck shaft angle (NSA) were recorded for osteoporotic group 121.55 and for control group 121.44. Pearson correlation coefficient t-test results showed a negative significant correlation between mineral density in the femoral neck in osteoporotic group and NSA (P<0.05). Considering the effect of weight and BMI in strength and bone density in the femoral neck, the mean of BMI and weight in osteoporotic group was lower compared to control group. Conclusion: according to the findings of this study, NSA is effective in predicting of the proximal femur BMD in osteoporotic group

Effect of dexamethasone on the endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS) genes expression during hepatic warm ischemia/reperfusion in rat

Background: Hepatic ischemia/reperfusion injury (I/RI) is a multifactorial pathophysiologic process which can lead to liver damage and dysfunction. This study examined the protective effect of dexamethasone on the gene expression of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) and on the liver tissue damage during warm hepatic I/R. Materials and Methods: A total of 32 male Wistar rats was randomly divided into four groups of eight: SHAM: the group receiving saline; DEX: the group receiving dexamethasone (8 mg/kg); I/R: Ischemia-reperfusion insulted group; and DEX + I/R: I/R group receiving dexamethasone. After 3 h of reperfusion followed by 60 min of ischemia, serum and ischemic tissue were collected. Serum was used to determine the hyaluronic acid (HA), aspartate and alanine aminotransferases (AST and ALT). To evaluate the eNOS and ET-1 gene expression, the total RNA was extracted from the liver tissue, cDNA was synthesized and real-time PCR was performed. Tissue staining was performed by the Hematoxylin and Eosin stain. Results: I/R increased serum AST, ALT and HA in I/R group compared with that in the SHAM group (P < 0.001). Dexamethasone significantly reduced the indicators in DEX + IR group (P < 0.001). In addition, the gene expression of the eNOS and ET-1 increased during I/R. Dexamethasone could significantly decrease the ET-1, but not eNOS gene expression in the DEX + IR group. Conclusions: Dexamethasone can decline hepatic I/RI by protecting the sinusoidal endothelial glycocalyx and modifying the expression of ET-1. Given that the reactive oxygen species (ROS) are the main cause of glycocalyx degradation and ET-1 is the regulator of hepatic perfusion, thus, dexamethasone has antioxidant properties and helps proper hepatic perfusion after ischemia to maintain

Using Hydroxyapatite-Gelatin Scaffold Seeded with Bone Marrow Stromal Cells as a Bone Graft in Animal Model

Background: Nowadays, composite scaffolds with some desired characteristics have a numerous applications in hard tissue engineering. In present study, the role of composite hydroxyapatite - gelatin was examined in both alone and coated by Bone Marrow Stromal Stem Cells (BMSCs) conditions in the process of healing bone defects, reduction of time repair and the immune response of body by laboratory studies (in vitro) and in vivo on the skull of adult rats as well. Materials and Methods: In present study, nano-hydroxyapatite powder and gelatin were used to provide nano-hydroxyapatite-gelatin scaffold, BMSCs were isolated by Flushing method. Fifteen adult male Wistar rats weighing 250-200 g were used. Studing groups included bone defect with hydroxyapatite-gelatin scaffold, bone defect with hydroxyapatite-gelatin with BMSCs and bone defects without scaffolding as a controlwhich were examined after a week and a month after surgery. MTT assay was used in order to evaluation of biocompatibility of scaffolds. To confirm the healing progress trend and the presence of inflammatory cells we used hematoxylin-eosin and we used Masson's trichrome staining in order to study of synthesis of collagen fibers. Results: The results of MTT showed that the scaffold has no toxic effects on stromal cells. The first signs of ossification in hydroxyapatite-gelatin with BMSCs cells group, appeared in the first week. However, in the fourth week, ossification was completed and the scaffold remaining was found as embedded islands in the spongy bone tissue. The greatest number of lymphocytes was observed in the experimental group after one week of planting scaffold. Conclusion: it seems that Hydroxyapatite-gelatin scaffold coated with BMSCs cells has a potential role in the healing process of bone and it can be suitable as a therapeutic strategy to repair extensive bone lesions