elastin and Body-Weight

Topics: Animals; Biological Products; Blood Pressure; Body Weight; Breast Neoplasms; Capillary Permeability; Disease Models, Animal; Elastin; Female; Gene Expression; Glomerular Filtration Rate; Heterografts; Humans; Hypotension; Mice; Molecular Mimicry; Neovascularization, Pathologic; Neovascularization, Physiologic; Rats; Rats, Sprague-Dawley; Recombinant Fusion Proteins; Renal Insufficiency, Chronic; Swine; Toxicity Tests, Chronic; Vascular Endothelial Growth Factor A; X-Ray Microtomography

Vegetable oils such as palm oil (enriched in saturated fatty acids, SFA) and high-oleic-acid sunflower oil (HOSO, containing mainly monounsaturated fatty acids, MUFA) have emerged as the most common replacements for trans-fats in the food industry. The aim of this study is to analyze the impact of SFA and MUFA-enriched high-fat (HF) diets on endothelial function, vascular remodeling, and arterial stiffness compared to commercial HF diets. Five-week-old male C57BL6J mice were fed a standard (SD), a HF diet enriched with SFA (saturated oil-enriched Food, SOLF), a HF diet enriched with MUFA (unsaturated oil-enriched Food, UOLF), or a commercial HF diet for 8 weeks. Vascular function was analyzed in the thoracic aorta. Structural and mechanical parameters were assessed in mesenteric arteries by pressure myography. SOLF, UOLF, and HF diet reduced contractile responses to phenylephrine and induced endothelial dysfunction in the thoracic aorta. A significant increase in the β-index, and thus in arterial stiffness, was also detected in mesenteric arteries from the three HF groups, due to enhanced deposition of collagen in the vascular wall. SOLF also induced hypotrophic inward remodeling. In conclusion, these data demonstrate a deleterious effect of HF feeding on obesity-related vascular alterations that is exacerbated by SFA.

Topics: Animals; Aorta, Thoracic; Arteries; Body Weight; Collagen; Diet, High-Fat; Dietary Fats; Dietary Fats, Unsaturated; Elastin; Fatty Acids; Fatty Acids, Monounsaturated; Fuchs' Endothelial Dystrophy; Glucose; Male; Mice; Mice, Inbred C57BL; Nitric Oxide; Oleic Acid; Plant Oils; Sunflower Oil; Vascular Remodeling; Vascular Stiffness

Extensive burn may cause acute resistance to insulin, which accentuates hypermetabolism, impairs glucose metabolism, immune dysfunction and risks of sepsis. To minimize these effects, insulin is used as a treatment. The purpose was to analyze the collagen-elastic arrangement effects of insulin on the burned skin. Wistar rats were assigned in groups: control (C); control with insulin (C + I); scald burn injury (SBI); and SBI with insulin (SBI+ I). SBI were submitted to 45% total body surface area burn and the insulin-treated groups received insulin (5 UI/Kg/day) for 4 or 14 days (d). Insulin levels, glucose tolerance test and HOMA index were determined. The skin sections were analyzed for histophatological and morphoquantitative data. Histopathological findings showed increased reepithelization of SBI+ I and formation of a new muscle layer after 14 days. In the collagen-elastic arrangement, insulin for 4 days increased the volume fraction (Vv) of thin collagen and elastic fibers. After 14 days, independently of injury, insulin decreased the elastic fibers. Insulin was able to reverse damages in the collagen-elastic rearrangement and stimulate reepithelization after 4 days. Untreated scald-burned animals showed higher Vv of thick collagen after 4 days, while those treated had a higher Vv of thin collagen. The Vv of elastic fibers was increased in SBI+ I for 4 days. In conclusion, insulin treatment was able to stimulate reepithelization. It also reversed the damages to the collagen-elastic arrangement in the scald-burned group, improving the organization of thin collagen and increasing the Vv of elastic fibers in the injured group treated with insulin for a short time, that is, for 4 days.

Topics: Animals; Area Under Curve; Body Weight; Burns; Collagen; Drinking Behavior; Elastin; Feeding Behavior; Glucose; Insulin; Male; Rats, Wistar; Re-Epithelialization; Skin

Abdominal aortic aneurysm (AAA) is a vascular disease characterized by the weakening of the vascular walls and the progressive dilation of the abdominal aorta. Nicotine, a primary component of cigarette smoke, is associated with AAA development and rupture. Nicotine induces AAA development by weakening vascular walls. However, little is known about preventive methods using functional food factors for nicotine-induced vascular destruction. Sesamin and sesamolin are functional food factors that are fat-soluble lignans found in Sesamum indicum seeds. Previous reports indicated that sesamin and sesamolin have anti-oxidative and anti-inflammatory effects. In this study, we evaluated the effects of sesamin and sesamolin-rich sesame extract on the weakening of vascular walls in nicotine-administered mice. Sesame extract attenuated the degradation of collagen and elastin fibers caused by nicotine. In addition, sesame extract decreased the area positive for matrix metalloproteinase 12 (MMP-12) and oxidative stress in the vascular walls. These results suggest that sesame extract may decrease the weakening of vascular walls by suppressing the nicotine-induced degradation of collagen and elastin fibers. Sesame extract may be effective in preventing AAA development by decreasing both, MMP-12 expression and oxidative stress in vascular walls.

Topics: Animals; Aorta, Thoracic; Aortic Aneurysm, Abdominal; Body Weight; Collagen; Dioxoles; Eating; Elastin; Lignans; Male; Matrix Metalloproteinase 12; Mice, Inbred C57BL; Nicotine; Oxidative Stress; Plant Extracts; Sesamum

Ascending aorta aneurysms (AsAA) are associated with a degeneration of the aortic wall tissue, which leads to changes in tissue mechanical properties. Risk factors for the development of the AsAA disease are recognized in patient age and gender, valve type, hypertension, diabetes mellitus, smoking history, and a prior diagnosis of Marfan syndrome. The present study aims to assess how such clinico-pathological factors can affect the mechanical properties of human dilated ascending aorta. Specimens of AsAA are excised from 68 patients who underwent elective AsAA surgical repair and stretched until rupture during the execution of uniaxial tensile tests. Experimental stress-stretch curves are used to determine tissue mechanical properties (stress and stretch at failure point and at transition point, low and high elastic modulus). Data are divided into groups according to region (anterior vs posterior), direction (circumferential vs longitudinal), and then according to age (young vs old), gender (male vs female), valve type (tricuspid aortic valve, TAV, vs bicuspid aortic valve, BAV), and presence of hypertension, diabetes mellitus, and/or Marfan syndrome (yes/no). Moreover, data are grouped according to the critical value of body mass index (BMI), maximum AsAA diameter, and aortic stiffness index (ASI), respectively. Finally, a non-parametric statistical analysis is performed to find possible significant differences and correlations between mechanical properties and clinico-pathological data. Our results confirm the anisotropy and heterogeneity of the AsAA tissue and highlight that ageing and hypertension make the AsAA tissue weaker and less extensible, whereas the valve type affects the tissue strength with higher values in BAV than in TAV patients. No effects of gender, critical BMI, critical maximum AsAA diameter, critical ASI, smoking status, and presence of diabetes mellitus, and Marfan syndrome are evidenced.

Topics: Aged; Anisotropy; Aorta; Aortic Aneurysm, Thoracic; Aortic Valve; Bicuspid Aortic Valve Disease; Biomechanical Phenomena; Body Mass Index; Body Weight; Collagen; Diabetes Mellitus; Elastin; Female; Heart Valve Diseases; Humans; Hypertension; Male; Marfan Syndrome; Middle Aged; Models, Statistical; Risk Factors; Stress, Mechanical; Tensile Strength; Vascular Stiffness

Acute lung injury (ALI) is characterized by hypoxemia, enhanced permeability of the air-blood barrier, and pulmonary edema. Particularly in the elderly, ALI is associated with increased morbidity and mortality. The reasons for this, however, are poorly understood. We hypothesized that age-related changes in pulmonary structure, function, and inflammation lead to a worse prognosis in ALI. ALI was induced in young (10 wk old) and old (18 mo old) male C57BL/6 mice by intranasal application of 2.5 mg lipopolysaccharide (LPS)/kg body wt or saline (control mice). After 24 h, lung function was assessed, and lungs were either processed for stereological or inflammatory analysis, such as bronchoalveolar lavage fluid (BALF) cytometry and qPCR. Both young and old mice developed severe signs of ALI, including alveolar and septal edema and enhanced inflammatory BALF cells. However, the pathology of ALI was more pronounced in old compared with young mice with nearly sixfold higher BALF protein concentration, twice the number of neutrophils, and significantly higher expression of neutrophil chemokine Cxcl1, adhesion molecule Icam-1, and metalloprotease-9, whereas the expression of tight junction protein occludin significantly decreased. The old LPS mice had thicker alveolar septa attributable to higher volumes of interstitial cells and extracellular matrix. Tissue resistance and elastance reflected observed changes at the ultrastructural level in the lung parenchyma in ALI of young and old mice. In summary, the pathology of ALI with advanced age in mice is characterized by a greater neutrophilic inflammation, leakier air-blood barrier, and altered lung function, which is in line with findings in elderly patients.

Topics: Acute Lung Injury; Aging; Animals; Blood-Air Barrier; Body Weight; Bronchoalveolar Lavage Fluid; Cell Count; Collagen; Disease Progression; Elastin; Extracellular Matrix; Flow Cytometry; Gene Expression Regulation; Lipopolysaccharides; Lung; Male; Mice, Inbred C57BL; Pneumonia; Pulmonary Alveoli; Respiratory Function Tests

Topics: Aging; Animals; Aorta; Biomechanical Phenomena; Blood Pressure; Body Weight; Collagen; Elastic Tissue; Elastin; Extracellular Matrix; Glycation End Products, Advanced; Male; Mice, Inbred C57BL; Minoxidil; Organ Size; RNA, Messenger

Antenatal inflammation and preterm birth are associated with the development of airway diseases such as wheezing and asthma. Utilizing a newborn mouse model, we assessed the effects of maternal inflammation and postnatal hyperoxia on the neonatal airway.. Pregnant C57/Bl6 dams were injected with lipopolysaccharide (LPS) or saline on embryonic day 16. Offspring were placed in room air or hyperoxia (50% O2) for 7 d and then returned to normoxia. Airway mechanics, histology, and laser capture micro-dissection (LCM) were performed.. At postnatal day 21, maternal LPS- and 50% O2-exposed pups exhibited increased resistance and decreased compliance compared to 21% O2 pups; however their effects were not synergistic. LPS and hyperoxia each increased the thickness of airway smooth muscle (ASM), but not the airway epithelial layer. Structural changes were largely limited to the conducting airways. Upregulation of inflammatory markers in the lung was observed at birth. LCM revealed increased collagen-3, transforming growth factor β, and connective tissue growth factor expression with LPS and hyperoxia within the ASM layer.. These novel studies provide functional, structural, and molecular evidence that antenatal inflammation is detrimental to the developing airway. Exposure to moderate hyperoxia does not exacerbate LPS effects on the airway.

Topics: Airway Remodeling; Animals; Animals, Newborn; Body Weight; Collagen; Disease Models, Animal; Dose-Response Relationship, Drug; Elastin; Female; Hyperoxia; Inflammation; Lipopolysaccharides; Lung; Methacholine Chloride; Mice; Mice, Inbred C57BL; Oxygen; Pregnancy; Pregnancy, Animal; Respiration; Respiratory System

Extremely preterm infants often receive mechanical ventilation (MV), which can contribute to bronchopulmonary dysplasia (BPD). However, the effects of MV alone on the extremely preterm lung and the lung's capacity for repair are poorly understood.. To characterise lung injury induced by MV alone, and mechanisms of injury and repair, in extremely preterm lungs and to compare them with very preterm lungs.. Extremely preterm lambs (0.75 of term) were transiently exposed by hysterotomy and underwent 2 h of injurious MV. Lungs were collected 24 h and at 15 d after MV. Immunohistochemistry and morphometry were used to characterise injury and repair processes. qRT-PCR was performed on extremely and very preterm (0.85 of term) lungs 24 h after MV to assess molecular injury and repair responses.. 24 h after MV at 0.75 of term, lung parenchyma and bronchioles were severely injured; tissue space and myofibroblast density were increased, collagen and elastin fibres were deformed and secondary crest density was reduced. Bronchioles contained debris and their epithelium was injured and thickened. 24 h after MV at 0.75 and 0.85 of term, mRNA expression of potential mediators of lung repair were significantly increased. By 15 days after MV, most lung injury had resolved without treatment.. Extremely immature lungs, particularly bronchioles, are severely injured by 2 h of MV. In the absence of continued ventilation these injured lungs are capable of repair. At 24 h after MV, genes associated with injurious MV are unaltered, while potential repair genes are activated in both extremely and very preterm lungs.

Topics: Animals; Blood Gas Analysis; Body Weight; Bronchioles; Cell Proliferation; Collagen; DNA; Elastin; Electrolytes; Fetal Blood; Gene Expression Regulation, Developmental; Lung; Myofibroblasts; Necrosis; Organ Size; Premature Birth; Respiration, Artificial; RNA, Messenger; Ventilator-Induced Lung Injury; Wound Healing

The mechanisms by which tracheal occlusion (TO) improves alveolarization in congenital diaphragmatic hernia (CDH) are incompletely understood. Therefore transcriptional and histological effects of TO on alveolarization were studied in the rabbit model for CDH. The question of the best normalization strategy for gene expression analysis was also addressed.. Fetal rabbits were randomized for CDH or sham operation on gestational day 23/31 and for TO or sham operation on day 28/31 resulting in four study groups. Untouched littermates were added. At term and before lung harvest, fetuses were subjected to mechanical ventilation or not. Quantitative real-time PCR was performed on lungs from 4-5 fetuses of each group with and without previous ventilation. Stability of ten housekeeping genes (HKGs) and optimal number of HKGs for normalization were determined, followed by assessment of HKG expression levels. Expression levels of eleven target genes were studied in ventilated lungs, including genes regulating elastogenesis, cell-environment interactions, and thinning of alveolar walls. Elastic staining, immunohistochemistry and Western blotting completed gene analysis.. Regarding HKG expression, TO increased β-actin and β-subunit of ATP synthase. Mechanical ventilation increased β-actin and β2-microglobulin. Flavoprotein subunit of succinate dehydrogenase and DNA topoisomerase were the most stable HKGs. CDH lungs showed disorganized elastin deposition with lower levels for tropoelastin, fibulin-5, tenascin-C, and α6-integrin. After TO, CDH lungs displayed a normal pattern of elastin distribution with increased levels for tropoelastin, fibulin-5, tenascin-C, α6-integrin, ß1-integrin, lysyl oxidase, and drebrin. TO increased transcription and immunoreactivity of tissue inhibitor of metalloproteinase-1.. Experimental TO might improve alveolarization through the mechanoregulation of crucial genes for late lung development. However part of the transcriptional changes involved genes that were not affected in CDH, raising the question of TO-induced disturbances of alveolar remodeling. Attention should also be paid to selection of HKGs for studies on mechanotransduction-mediated gene expressions.

Topics: Animals; Body Weight; Elastin; Female; Gene Expression Regulation; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Lung; Matrix Metalloproteinases; Rabbits; Random Allocation; Trachea

Necrotic death of macrophages has long been known to be present in atherosclerotic lesions but has not been studied. We examined the role of receptor interacting protein (RIP) 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3(-/-);Ldlr(-/-) mice were no different from RIP3(+/+);Ldlr(-/-) mice in early atherosclerosis but had significant reduction in advanced atherosclerotic lesions. Similar results were observed in Apoe(-/-) background mice. Bone marrow transplantation revealed that loss of RIP3 expression from bone-marrow-derived cells is responsible for the reduced disease progression. While no difference was found in apoptosis between RIP3(-/-);Ldlr(-/-) and RIP3(+/+);Ldlr(-/-) mice, electron microscopy revealed a significant reduction of macrophage primary necrosis in the advanced lesions of RIP3(-/-) mice. In vitro cellular studies showed that RIP3 deletion had no effect on oxidized low-density lipoprotein (LDL)-induced macrophage apoptosis, but prevented macrophage primary necrosis occurring in response to oxidized LDL under caspase inhibition or RIP3 overexpression conditions. RIP3-dependent necrosis is not postapoptotic, and the increased primary necrosis in advanced atherosclerotic lesions most likely resulted from the increase of RIP3 expression. Our data demonstrate that primary necrosis of macrophages is proatherogenic during advanced atherosclerosis development.

Topics: Animals; Apolipoproteins E; Apoptosis; Atherosclerosis; Biomarkers; Body Weight; Bone Marrow Cells; Bone Marrow Transplantation; Caspase 8; Caspase Inhibitors; Cell Shape; Cholesterol; Collagen; Cytokines; Elastin; Female; Inflammation; Lipoproteins, LDL; Macrophages; Mice; Microdissection; Necrosis; Receptor-Interacting Protein Serine-Threonine Kinases; Receptors, LDL; RNA, Messenger; Up-Regulation

The interactions between the effects of the sympathetic nervous system (SNS) and angiotensin II (ANG II) on vascular extracellular matrix (ECM) synthesis were determined in rats. The mRNA and protein content of collagen I, collagen III and elastin in the abdominal aorta (AA) and femoral artery (FA) was investigated in Wistar-Kyoto rats treated for 5 weeks with guanethidine, a sympathoplegic, losartan, an ANG II AT1 receptor (AT1R) blocker, or both. The effects of noradrenaline (NE) and ANG II on collagen III and elastin mRNA, and the receptor involved, were tested in cultured vascular smooth muscle cells (VSMCs) in vitro. Guanethidine increased collagen types I and III and decreased elastin, while losartan had an opposite effect, although without effect on collagen III. The combination of treatments abrogated changes induced by simple treatment with collagen I and elastin, but increased collagen III mRNA in AA and not in FA. NE stimulated collagen III mRNA via β receptors and elastin via α1 and α2 receptors. ANG II stimulated collagen III but inhibited elastin mRNA via AT1R. Overall, SNS and ANG II exert opposite and antagonistic effects on major components of ECM in the vascular wall. This may be of relevance for the choice of a therapeutic strategy in vascular diseases.

Topics: Angiotensin II; Animals; Aorta, Abdominal; Blood Pressure; Blotting, Western; Body Weight; Collagen; Collagen Type I; Collagen Type III; Elastin; Extracellular Matrix; Femoral Artery; Gene Expression Regulation; Male; Models, Biological; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Norepinephrine; Rats; Rats, Inbred WKY; Real-Time Polymerase Chain Reaction

Survivors of moderate-to-severe bronchopulmonary dysplasia have impaired alveologenesis lasting at least into early adult life. The mechanisms underlying this long-term effect are unknown. We hypothesized that short-term inhibition of growth factor-mediated early alveolar formation would result in a long-term impairment of subsequent alveologenesis. Neonatal rats were injected daily with the platelet-derived growth factor (PDGF) receptor antagonist, imatinib mesylate, from day 1-7 of life, to inhibit the early alveolar formation occurring by in-growth of secondary crests into precursor saccules. The pups were then allowed to recover for 7, 14, 21, or 58 days. In imatinib-treated pups, DNA synthesis in total lung cells, and specifically in cells of secondary crests, was reduced at day 8 of life, had rebounded on day 14 of life but was then again reduced by day 28 of life. At day 8 of life, imatinib-treated pups had impaired alveologenesis as reflected by a decrease in secondary crests, an increase in alveolar size, and an overall decrease in both estimated alveolar number and generations compared with age-matched controls. No meaningful recovery was observed, even after a 21- or 58-day recovery period. The lungs of imatinib-treated pups had increased fibulin-5 content and an abnormal deposition of elastin. We conclude that reduced signaling through the PDGF pathways, at an early stage of alveologenesis, can result in long-lasting changes in lung architecture. A likely mechanism is through impaired formation of the elastin scaffold required for alveolarization.

Topics: Animals; Animals, Newborn; Benzamides; Blotting, Western; Body Weight; Bromodeoxyuridine; Cell Count; Densitometry; Elastin; Imatinib Mesylate; Organ Size; Organogenesis; Phosphorylation; Piperazines; Proto-Oncogene Proteins c-kit; Pulmonary Alveoli; Pyrimidines; Rats; Receptor, Platelet-Derived Growth Factor alpha; Receptor, Platelet-Derived Growth Factor beta; Time Factors

Increased arterial stiffness and blood pressure are characteristic of humans and adult mice with reduced elastin levels caused by aging or genetic disease. Direct associations have been shown between increased arterial stiffness and hypertension in humans, but it is not known whether changes in mechanical properties or increased blood pressure occur first. Using genetically modified mice with elastin haploinsufficiency (Eln(+/-)), we investigated the temporal relationship between arterial mechanical properties and blood pressure throughout postnatal development. Our results show that some mechanical properties are maintained constant regardless of elastin amounts. The peak diameter compliance for both genotypes occurs near the physiologic pressure at each age, which acts to provide maximum pulse dampening. The stress-strain relationships are similar between genotypes and become nonlinear near the systolic pressure for each age, which serves to limit distension under high pressure. Our results also show that some mechanical properties are affected by reduced elastin levels and that these changes occur before measurable changes in blood pressure. Eln(+/-) mice have decreased aortic diameter and compliance in ex vivo tests that are significant by postnatal day 7 and increased blood pressure that is not significant until postnatal day 14. This temporal relationship suggests that targeting large arteries to increase diameter or compliance may be an effective treatment for human hypertension.

Topics: Aging; Algorithms; Animals; Animals, Newborn; Aorta; Blood Pressure; Body Weight; Carotid Arteries; Compliance; Elasticity; Elastin; Extracellular Matrix; Female; Genotype; Linear Models; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Organ Size; Sex Characteristics; Stress, Mechanical; Ventricular Function, Left

Intrauterine growth restriction caused by uteroplacental insufficiency increases the risk of cardiovascular disease in adulthood. Vascular mechanisms in female offspring are poorly understood. The aim of this study was to investigate the effects of uteroplacental insufficiency on blood pressure, vascular reactivity and arterial stiffness in four vascular beds in female offspring born growth restricted. Uteroplacental insufficiency was induced on day 18 of gestation in Wistar Kyoto rats by bilateral uterine vessel ligation (Restricted) or sham surgery (Controls). Wire and pressure myography were used to test endothelial and smooth muscle function, and passive mechanical wall properties, respectively, in uterine, mesenteric, renal and femoral arteries of 18-month-old female offspring. Collagen and elastin fibres were quantified using circular crossed-polarized light microscopy and quantitative real time polymerase chain reaction. Restricted female offspring were born 10-15% smaller. Restricted females were normotensive, had plasma triglycerides 2-fold elevated and had uterine endothelial dysfunction, attributed to a 23% reduction in the maximal relaxation produced by endothelium-derived hyperpolarizing factor. Uterine artery stiffness was increased, with an augmented proportion of thick and decreased proportion of thin collagen fibres. Vascular reactivity and mechanical wall properties were preserved in mesenteric, renal and femoral arteries in growth restricted females. Female offspring born growth restricted have selective uterine artery endothelial dysfunction and increased wall stiffness. The preserved vascular function in other arteries may explain the lack of hypertension in these females. The uterine artery specific dysfunction has potential implications for impaired pregnancy adaptations and a compromised intrauterine environment of the next generation.

Topics: Animals; Arteries; Blood Pressure; Body Weight; Cardiovascular Diseases; Collagen; Elastin; Endothelium, Vascular; Female; Lipids; Litter Size; Muscle Relaxation; Muscle, Smooth, Vascular; Placental Insufficiency; Pregnancy; Rats; Rats, Inbred WKY; Risk; RNA; Uterus; Vascular Diseases

Elastolysis, collagenolysis and gelatinolysis are essential in the pathogenesis of tobacco smoke-induced emphysema; however, these activities have been scantily studied in emphysema secondary to woodsmoke. The aim of this study was to analyze elastolysis, collagenolysis and gelatinolysis, MMP-1, MMP-2, and MMP-9 expression, and apoptosis in guinea pigs exposed to smoke produced by 60 g/day of pine wood, 5 days/week, from 1 to 7 months. Histological analysis after 4 to 7 months in smoke exposed guinea pigs showed alveolar mononuclear phagocyte and lymphocytic peribronchiolar inflammation, epithelial and smooth muscle hyperplasia, and pulmonary arterial hypertension. Mild to moderate emphysematous lesions were observed in woodsmoke-exposed animals at 4 to 7 months by increase of mean linear intercepts. A higher percentage of whole blood carboxyhemoglobin (COHb) and elastolytic activity in bronchoalveolar lavage macrophages and lung tissue homogenates was observed at all times. Collagenolysis was increased after 4 to 7 months in woodsmoke-exposed animals, although collagen concentration did not change. Zymography revealed increase in lysis bands of the active MMP-2 and MMP-9 at 4 and 7 months in bronchoalveolar lavage fluid and lung tissue homogenate. Positive immunostaining for MMP-1 and MMP-9 was observed in epithelial cells and macrophages in wood exposed animals at 4 to 7 months. Real-time PCR showed MMP-2 and MMP-9 expression at 3 to 7 months in exposed animals. Furthermore, apoptosis was increased at all times in bronchoalveolar lavage macrophages and lung tissue from exposed animals. Results support a role of metalloproteinases and apoptosis in emphysema secondary to woodsmoke exposure.

Topics: Animals; Apoptosis; Body Weight; Bronchoalveolar Lavage Fluid; Carboxyhemoglobin; Cell Count; Collagen; Elastin; Gelatin; Guinea Pigs; Immunohistochemistry; Inhalation Exposure; Lung; Macrophages, Alveolar; Matrix Metalloproteinases; Particle Size; Particulate Matter; Pulmonary Emphysema; Reverse Transcriptase Polymerase Chain Reaction; Smoke; Time Factors; Wood

To investigate a putative role for semicarbazide-sensitive amine oxidase (SSAO) in arterial extracellular matrix (ECM) organization, we compared arteries of growing Brown Norway (BN) rats after chronic administration of semicarbazide (SCZ) and beta-aminopropionitrile (BAPN), two inhibitors with different properties and relative specificities for SSAO and lysyl oxidase (LOX). The BN model is particularly well adapted to evaluating effects of toxic compounds on the arterial elastic network. We measured aortic LOX and SSAO activities and quantified several ECM parameters. After a pilot study comparing doses previously studied and testing for additivity, we studied low and high equimolar doses of SCZ and BAPN. Both compounds similarly inhibited LOX, whereas SCZ inhibited SSAO far more effectively than BAPN. Both decreased carotid wall rupture pressure, increased tail tendon collagen solubility, decreased aortic insoluble elastin (% dry weight) and dose-dependently increased defects in the internal elastic lamina of abdominal aorta, iliac and renal arteries. Our results suggest that either these effects are mediated by LOX inhibition, SCZ being slightly more effective than BAPN in our conditions, or SSAO acts similarly to and in synergy with LOX on ECM, the greater SCZ effect reflecting the simultaneous inhibition of both enzymes. However, the high SCZ dose increased aortic collagen and ECM proteins other than insoluble elastin markedly more than did equimolar BAPN, possibly revealing a specific effect of SSAO inhibition. To discriminate between the two above possibilities, and to demonstrate unequivocally a specific effect of SSAO inhibition on ECM formation or organization, we must await availability of more specific inhibitors.

Topics: Amine Oxidase (Copper-Containing); Aminopropionitrile; Animals; Aorta, Thoracic; Body Weight; Carotid Arteries; Collagen; Drug Synergism; Elastin; Extracellular Matrix; Male; Pilot Projects; Protein-Lysine 6-Oxidase; Rats; Rats, Inbred BN; Semicarbazides

Mild or marginal vitamin A deficiency (MVAD) is still a serious and widespread public health problem in pregnant women and children in developing countries. This study investigated rat lung maturation from prenatal to adult stage during pregnancy and postnatal MVAD and the recovery after postnatal vitamin A supplementation (VAS). Adult female rats and their offspring were randomized into three groups. 1.. the mothers and offspring received a normal diet.2. MVAD: The mothers and offspring received a MVAD diet.3. VAS: the mothers received MVAD diet till parturition, and then received the normal diet. The offspring of the VAS group were given low-dose vitamin A from postnatal day 1 to day 7 and received the normal diet after weaning. The lung development, structure, and collagen and elastic fiber of offspring were monitored by morphometric analysis at age 1 d, 2 and 8 wk, respectively. Lower body weight, lung weight, reduced numbers of alveoli and total alveolar surface area as well as increased alveoli septa thickness was observed in MVAD compared to that in the control animals. Increased collagen deposits and decreasing elastic fiber were found in MVAD rats. However, all of these were significantly improved in VAS-treated animals. These data suggest that the rat lung is sensitive to MVAD during the developing stage. Early postnatal vitamin A supplementation can partially restore the normal lung structure.

Topics: Animals; Animals, Newborn; Body Weight; Collagen; Diet; Elastin; Female; Fetal Nutrition Disorders; Lung; Organ Size; Pregnancy; Pregnancy Complications; Rats; Rats, Wistar; Vitamin A; Vitamin A Deficiency

Matrix metalloprotease-9 (MMP-9) is increased in lung injury following hyperoxia exposure in neonatal mice, in association with impaired alveolar development. We studied the role of MMP-9 in the mechanism of hyperoxia-induced functional and histological changes in neonatal mouse lung. Reduced alveolarization with remodeling of ECM is a major morbidity component of oxidant injury in developing lung. MMP-9 mediates oxidant injury in developing lung causing altered lung remodeling. Five-day-old neonatal wild-type (WT) and MMP-9 (-/-) mice were exposed to hyperoxia for 8 days. The lungs were inflation fixed, and sections were examined for morphometry. The mean linear intercept and alveolar counts were evaluated. Immunohistochemistry for MMP-9 and elastin was performed. MMP-2, MMP-9, type I collagen, and tropoelastin were measured by Western blot analysis. Lung quasistatic compliance was studied in anaesthetized mice. MMP-2 and MMP-9 were significantly increased in lungs of WT mice exposed to hyperoxia compared with controls. Immunohistochemistry showed an increase in MMP-9 in mesenchyme and alveolar epithelium of hyperoxic lungs. The lungs of hyperoxia-exposed WT mice had less gas exchange surface area and were less compliant compared with room air-exposed WT and hyperoxia-exposed MMP-9 (-/-) mice. Type I collagen and tropoelastin were increased in hyperoxia-exposed WT with aberrant elastin staining. These changes were ameliorated in hyperoxia-exposed MMP-9 (-/-) mice. MMP-9 plays an important role in the structural changes consequent to oxygen-induced lung injury. Blocking MMP-9 activity may lead to novel therapeutic approaches in preventing bronchopulmonary dysplasia.

Topics: Animals; Animals, Newborn; Body Weight; Elastin; Hyperoxia; Lung; Matrix Metalloproteinase 9; Mice; Pulmonary Alveoli; Respiratory Distress Syndrome; Respiratory Function Tests

The number of men with type II diabetes-associated erectile dysfunction (ED) continues to grow rapidly; however, the majority of basic science studies has examined mechanisms of ED in animal models of type I diabetes. In this study, we first establish an in vivo mouse model of type II diabetic ED using the leptin receptor mutated db/db and wild-type control BKS mouse. Furthermore, we hypothesized that dual mechanistic impairments contribute to the impaired erectile function in the type II diabetic mouse, altered vasoreactivity, and venoocclusive disorder. In vivo erectile function was measured as intracavernosal pressure (ICP) normalized to mean arterial pressure (MAP) following electrical stimulation of the cavernosal nerve. Venoocclusion was assessed by the maintenance of elevated in vivo ICP following intracorporal saline infusion. Vasoreactivity of isolated cavernosum in response to contractile and dilatory stimulation was examined in vitro by myography. Collagen and elastin content were evaluated by quantification of hydroxyproline and desmosine, respectively, as well as by quantitative PCR and histological analysis of isolated cavernosum. Erectile function was significantly decreased in db/db vs. BKS mice in a manner consistent with impairments in venoocclusive ability and decreased inflow. Heightened vasoconstriction and attenuated dilation in cavernosum of db/db vs. BKS mice suggest an overall lowered relaxation ability and thus impaired filling of the cavernosal spaces. A decrease in desmosine and hydroxyproline as well as lowered mRNA levels for tropoelastin, fibrillin-1, and alpha1(I) collagen were detected. These vasoreactive and sinusoidal matrix alterations may alter tissue compliance dispensability, preventing the normal expansion necessary for erection.

Topics: Acetylcholine; Animals; Blood Glucose; Blood Pressure; Body Weight; Collagen; Desmosine; Diabetes Mellitus, Type 2; Disease Models, Animal; Elastin; Electric Stimulation; Erectile Dysfunction; Extracellular Matrix; Hydroxyproline; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Myography; Organ Size; Penis; Phenylephrine; Polymerase Chain Reaction; Receptors, Leptin; Regional Blood Flow; RNA, Messenger; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Veins

Blockade of the renin-angiotensin system (RAS) reduces cardiovascular morbidity and mortality in diabetic patients. Ang II-mediated generation of reactive oxygen species (ROS) has been suggested to be involved in several diabetic complications. We investigated whether the inhibition of Ang II production with an ACE inhibitor (ACEi) reduces oxidative stress and limits structural cardiovascular remodeling in a rat model of streptozotocin (STZ)-induced diabetes. Diabetic rats were treated for 7 weeks with an ACEi (lisinopril, 5 mg/kg/d), an antioxidant (N-acetyl-l-cysteine (NAC), 0.5 g/kg/d) and their combination. At sacrifice, ROS in the myocardium and thoracic aorta, LV myocyte number and size and aorta morphology were determined by quantitative histological methods. Superoxide and hydroxyl radical content, detected by dihydroethidium (DHE) and 8-hydroxydeoxyguanosine (8-OHdG), were 6.7 and 4.5-fold, respectively, higher in diabetic myocardium than in non-diabetic controls (p<0.001). The amount of superoxide was 5-fold higher in the thoracic aorta of diabetic rats compared to controls (p<0.001). Diabetes caused a modest increase in myocyte volume (+13%, p<0.01), a reduction of LV myocyte number (-43%, p<0.001), an accumulation of collagen around coronary arterioles (1.9-fold increase, p<0.01) and a decrease in arterial elastin/collagen ratio (-63%, p<0.001) compared to controls. Treatment with the ACEi attenuated ROS formation and prevented phenotypic changes in the heart (cardiomyocyte hypertrophy, perivascular fibrosis) and in the aorta of diabetic rats to the same extent as NAC. The absence of an additive effect, suggests a common mechanism of action, through the reduction of oxidative stress.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta, Thoracic; Body Weight; Cardiovascular System; Diabetes Mellitus, Experimental; Drinking; Elastin; Extracellular Space; Fibrosis; Heart Ventricles; Hemodynamics; Male; Myocardium; Myocytes, Cardiac; Oxidative Stress; Rats; Rats, Sprague-Dawley; Superoxides

Supravalvular aortic stenosis is an autosomal-dominant disease of elastin (Eln) insufficiency caused by loss-of-function mutations or gene deletion. Recently, we have modeled this disease in mice (Eln+/-) and found that Eln haploinsufficiency results in unexpected changes in cardiovascular hemodynamics and arterial wall structure. Eln+/- animals were found to be stably hypertensive from birth, with a mean arterial pressure 25-30 mmHg higher than their wild-type counterparts. The animals have only moderate cardiac hypertrophy and live a normal life span with no overt signs of degenerative vascular disease. Examination of arterial mechanical properties showed that the inner diameters of Eln+/- arteries were generally smaller than wild-type arteries at any given intravascular pressure. Because the Eln+/- mouse is hypertensive, however, the effective arterial working diameter is comparable to that of the normotensive wild-type animal. Physiological studies indicate a role for the renin-angiotensin system in maintaining the hypertensive state. The association of hypertension with elastin haploinsufficiency in humans and mice strongly suggests that elastin and other proteins of the elastic fiber should be considered as causal genes for essential hypertension.

Topics: Adaptation, Physiological; Animals; Arteries; Blood Pressure; Body Weight; Cardiac Output; Collagen; Elastin; Heart Rate; Hypertension; Mice; Mice, Inbred C57BL; Muscle, Smooth, Vascular; Phenylephrine; Proliferating Cell Nuclear Antigen; Renin-Angiotensin System

Topics: Animals; Body Weight; Collagen Type I; Collagen Type III; Disease Models, Animal; Elastin; Extracellular Matrix Proteins; Female; Fetal Diseases; Fibrillins; Fibronectins; Gene Expression; Hydronephrosis; Ligation; Male; Microfilament Proteins; Organ Size; Pregnancy; RNA, Messenger; Sex Factors; Sheep; Ultrasonography; Urinary Bladder; Urinary Bladder Neck Obstruction

Collagen and elastin are major components of the aortic extracellular matrix and crucial in determining the stiffness of the aorta. We recently showed that growth hormone (GH) changes the mechanical properties, content and composition of aortic collagen from young rats. In the present study, the effect of GH on aorta from old rats was investigated. Old female rats (18(1/2)-20(1/2) months) were injected with either GH (5 mg/kg per day; n=15) or vehicle (n=14) for 80 days. Mechanical and biochemical properties of the thoracic aorta were investigated. Long-term GH injections increased the body weight of female rats by 47% accompanied by a threefold increase in serum IGF-I. The diameter of the aorta was increased by 5%, resulting in a 10% increase in the cross-section of the aortic lumen. Growth hormone increased the content of collagen per sample by 6% and increased the amount of type I collagen relative to type III collagen. No changes in the mechanical properties or elastin content per sample were found. In conclusion, GH induced a substantial growth of old rats. However, although the diameter and the collagen content were increased, the mechanical properties of the aorta were preserved in the GH-injected rats.

Topics: Aging; Animals; Aorta, Thoracic; Body Weight; Collagen Type I; Collagen Type III; Elastin; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Rats; Rats, Wistar

With aging, the aortic wall becomes stiffer. This could be because of changes in wall stress or composition. We investigated whether a specific change in wall composition, ie, accumulation of advanced glycation end products (AGEs) on the extracellular matrix, is a major factor. We measured aortic mechanics, geometry, and composition in 3-, 10-, 15-, 20-, and 30-month-old inbred normotensive Wistar-Glaxo/Rijswick rats and in a group of 30-month-old rats treated from 20 months onward with aminoguanidine (AG, 42 mg/kg per day), an inhibitor of AGE formation. Thoracoabdominal aortic (pressure) pulse-wave velocity (PWV) increased progressively with age (44% from 3 to 30 months). This age-related increase in aortic PWV was not related to changes in wall stress. For all ages, central (and peripheral) aortic mean blood pressures were not statistically different. Dilatation occurred (18% increase in internal diameter from 3 to 30 months), but this was accompanied by outward hypertrophic remodeling, with an increase in the medial cross-sectional area of 95% and in the ratio of medial thickness to internal diameter of 29%. Wall stress decreased with age (-34%). There was an increase in the ratio of elastic modulus (calculated from the Moens-Korteweg equation) to wall stress (calculated from the Lamé equation, 117% from 3 to 30 months), suggesting that a change in the composition of the wall is responsible for the age-linked increase in wall stiffness. Dry weight decreased slightly but significantly (-14%) with age. Total protein, elastin, collagen, and nonscleroprotein protein [total-(elastin+collagen)] contents did not change with age, but calculated densities of all 4 were halved (as the medial cross-sectional area doubled). The elastin/collagen ratio was statistically similar at all ages. The only significant effect of AG treatment was a fall in PWV (-20%), leading to a fall in the elastic modulus/wall stress ratio (-27% at 10 months of AG treatment versus 30 months of no treatment). In conclusion, the age-related increase in aortic wall stiffness is prevented by 10 months of treatment with AG, which has no effect on wall stress or composition, suggesting that AG may improve aortic wall stiffness by lowering the degree of AGE-induced cross-linking of the extracellular matrix scleroproteins, such as collagen.

Topics: Aging; Animals; Aorta; Aorta, Thoracic; Blood Glucose; Blood Pressure; Body Weight; Calcium; Collagen; Elastin; Guanidines; Proteins; Pulse; Rats; Rats, Inbred Strains

Sustained fetal tracheal occlusion (TO) results in accelerated lung growth but causes severe type II cell depletion. Temporary TO fails to cause lung growth in a congenital diaphragmatic hernia (CDH) model but preserves type II cells and corrects pulmonary hypertension. Herein, we study the pulmonary vascular changes caused by temporary TO.. CDH was created in 12 fetal lambs (65-70 d; term, 145 days). In 6 lambs, the trachea was occluded for 2 weeks (CDH + TO; 108-122 d). Animals were killed at 136 days. The lungs were processed with elastin stains and anti-alpha-smooth muscle actin antibody. Partial or circumferential presence of inner and outer elastic lamina was used to determine muscularization of pulmonary arterioles. The percent of medial wall thickness was plotted against vessel diameter for each group.. Lung weight/body weight was smaller in lambs with CDH (1. 35% +/- 0.56%) and CDH + TO (1.70% +/- 0.34%) than in control lambs (3.55% +/- 0.56%; P <.05, single-factor analysis of variance). The smallest muscularized vessel was 113 +/- 50 microm, and the largest nonmuscularized vessel was 138 +/- 49 microm in lambs with CDH, significantly different from control lambs (185 +/- 69 microm and 350 +/- 116 microm, respectively) and lambs with CDH + TO (185 +/- 97 microm and 245 +/- 100 microm, respectively; P <.05). In lambs with CDH, only 25% of vessels of less than 60 microm were nonmuscularized, compared with 81% in control lambs (P <.05) and 74% in lambs with CDH + TO.Conclusions. Temporary tracheal occlusion, from 108 to 122 days, corrects the abnormal muscularization of pulmonary arterioles seen in CDH. These morphometric findings parallel physiologic results at birth and further suggest that short-term occlusion, which preserves surfactant-producing type II pneumocytes without lung growth, may be sufficient to improve neonatal outcome of diaphragmatic hernia.

Topics: Actins; Animals; Arterioles; Body Weight; Elastin; Female; Hernia, Diaphragmatic; Hypertension, Pulmonary; Lung; Organ Size; Pregnancy; Pulmonary Circulation; Sheep; Trachea

The effects of estrogen replacement therapy in menopausal women are more obvious on bones than on the cardiovascular system. The optimal estrogen dosage may differ in these different parts of the body. In hypertensive rats, low doses have been shown to reduce arterial collagen and stiffness, whereas higher dosages are required for osteoprotection. From 4 to 20 weeks of age, female spontaneously hypertensive rats (SHRs) were divided into four groups: without ovariectomy, under placebo or 17 beta-estradiol (10 micrograms/kg/day), and with ovariectomy under either placebo or 17 beta-estradiol (same dosage). Serial tail systolic blood pressure measurements were performed, and histomorphometry of the thoracic aorta was determined at the end of the study. Under estrogen, blood pressure was unchanged, whereas the aortic wall-to-lumen ratio was increased, particularly in the presence of ovariectomy. The elastin to collagen ratio was significantly decreased, due both to a decrease in elastin and an increase in collagen density, with no change in media thickness. The latter findings were not observed when ovariectomy was performed. Independent of changes in wall stress, high-dose estrogen increases the aortic extracellular matrix in female SHRs. This increase may be reversed in the presence of ovariectomy, suggesting that estrogen was not the only gonadal factor responsible for altered vascular structure and function.

Topics: Animals; Aorta, Thoracic; Blood Pressure; Body Weight; Elastin; Estradiol; Extracellular Matrix; Female; Hemodynamics; Hormone Replacement Therapy; Myocardium; Osteoporosis; Ovariectomy; Rats; Rats, Inbred SHR

To study the alteration in the biomechanical properties of the thoracic aorta and its composition in young normotensive Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP).. The in-vitro biomechanical properties of the aorta in 4- and 12-week-old SHRSP were determined by means of a tensile testing machine and compared with those of the SHR and WKY rats; in addition, a biochemical analysis of collagen, elastin and advanced glycation endproducts was performed.. The aortic biomechanical properties were altered in the 4- and 12-week-old SHRSP, compared with age-matched WKY rats and SHR. The maximum stress in the 12-week-old SHRSP was reduced by 27% compared with the normotensive WKY rats, and by 26% compared with the SHR. The maximum strain values in the 4- and 12-week-old SHRSP were lower than those in the age-matched WKY rats, by 12 and 9% respectively, whereas this value in the 12-week-old SHR was significantly increased (by 26%) compared with the age-matched WKY rats. No differences were observed in the aortic contents of collagen and elastin between the SHRSP and SHR. However, the extractability of collagen by pepsin digestion in the 12-week-old SHRSP was lower than that in the age-matched SHR and WKY rats, and a significantly larger accumulation of advanced glycation endproducts was observed in the 12-week-old SHRSP than in the age-matched SHR and WKY rats, suggesting a greater formation of collagen-derived cross-links in SHRSP.. From these results, we conclude that decreased aortic distensibility and mechanical strength values are partly related to the greater formation of collagen-derived cross-links in 12-week-old SHRSP, and that the mechanical properties in SHRSP may be the result not only of the larger formation of collagen-derived cross-links but also of primary defects, since the aortic mechanical strength value was decreased even in 4-week-old SHRSP.

Topics: Animals; Aorta, Thoracic; Biomechanical Phenomena; Blood Glucose; Blood Pressure; Body Weight; Collagen; Elastin; Glycation End Products, Advanced; Hypertension; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY

We hypothesized that age-linked changes in the composition and elastic properties of the arterial wall occur earlier in hypertensive than in normotensive rats. We evaluated the consequences of hypertension and aging on aortic mechanics, geometry, and composition in 3-, 9-, and 15-month-old awake Wistar-Kyoto rats (WKY) (normotensive) and spontaneously hypertensive rats (SHR) (hypertensive). The elastic modulus of the thoracic aorta, calculated from aortic pulse wave velocity and geometry, was higher in young and adult SHR than in age-matched WKY, as was wall stress; however, isobaric pulse wave velocity and pulse wave velocity-pressure curves were similar. Elastic modulus, isobaric pulse wave velocity, and the slope of the pulse wave velocity-pressure curve dramatically increased in old SHR compared with age-matched WKY; there was no further elevation of blood pressure or wall thickness. Fibrosis did not develop with age in SHR, and the ratio of elastin to collagen decreased in a similar fashion with aging in both strains. In conclusion, although elastic properties of the aortic wall are not intrinsically modified in young and adult SHR in comparison to age-matched WKY, aging is associated with a dramatic stiffening of the aortic wall in old SHR but not in WKY. Changes in blood pressure, aortic wall geometry, or scleroprotein composition do not appear to explain this age-linked aortic stiffening in SHR, suggesting that other mechanisms of disorganization of the media may be involved.

Topics: Aging; Animals; Aorta, Thoracic; Blood Pressure; Body Weight; Elasticity; Elastin; Heart Rate; Hypertension; In Vitro Techniques; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Altered vascular mechanics resulting from changes in collagen and integrins may influence resistance artery structure and function and, therefore, peripheral resistance and blood pressure in spontaneously hypertensive rats (SHR).. Effects of age, angiotensin-converting enzyme inhibition (fosinopril, 10 to 30 mg/kg per day), and AT(1)-receptor antagonism (irbesartan, 50 mg/kg per day) on vascular structure, mechanics, and composition were assessed in SHR. Systolic blood pressure was elevated in young SHR (130+/-2 mm Hg) compared with Wistar-Kyoto (WKY) rats (106+/-2 mm Hg). In adult SHR, the rise in systolic blood pressure (44+/-3 mm Hg) was blunted by fosinopril (18+/-1 mm Hg) and irbesartan (9+/-3 mm Hg). Lumen diameter of mesenteric resistance arteries was smaller and media/lumen ratio was greater in young and adult SHR versus WKY rats. Growth index was 24% in untreated adult SHR versus WKY rats; these values were -35% for fosinopril-treated and -29% for irbesartan-treated SHR versus untreated SHR. Isobaric wall stiffness was normal despite increased stiffness of wall components in adult SHR vessels. Irbesartan partially prevented stiffening of wall components in SHR. The collagen/elastin ratio was greater in adult SHR vessels (6.5+/-1.3) than in WKY (3.2+/-0.4) vessels. Expression of alpha(v)beta(3) and alpha(5)beta(1) integrins was increased in SHR aged 20 versus 6 weeks. Expression of alpha(5)beta(1) integrins was lower in young SHR, and alpha(v)beta(3) integrins were overexpressed in adult SHR versus WKY rats. Irbesartan and fosinopril attenuated differences in the collagen/elastin ratio and integrin expression.. Wall components of mesenteric resistance arteries stiffen with age in SHR. Interrupting the renin-angiotensin system has normalizing effects on integrin expression and composition, stiffness, and growth of the arterial wall.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Biphenyl Compounds; Blood Pressure; Body Weight; Collagen; Elastin; Fosinopril; Hypertension; Integrins; Irbesartan; Male; Mesenteric Arteries; Oligopeptides; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Tetrazoles; Vascular Resistance

Spontaneous rupture of the internal elastic lamina (IEL) occurs in some arteries of the rat during growth and aging. Inbred, normotensive, Brown Norway (BN) rats are particularly susceptible to rupture of the IEL, especially in the abdominal aorta (AA). Preliminary experiments showed that different angiotensin-converting enzyme (ACE) inhibitors protect against rupture of the IEL in the BN rat to a greater extent than hydralazine, suggesting a role of the renin-angiotensin system (RAS) in this phenomenon. To explore this possibility, we have treated male BN rats from 4.5 to 14 weeks of age with either enalapril or losartan (both at 1, 3, and 10 mg x kg(-1) x d(-1)) or with the calcium antagonists mibefradil (at 3, 10, 30, and 45 mg x kg(-1) x d(-1)) and amlodipine (at 30 mg x kg(-1) x d(-1)). Systolic blood pressure (SBP) was measured weekly, and at the end of treatment we (1) recorded body and heart weights, (2) measured various parameters of the RAS in plasma, (3) quantified interruptions in the IEL on "en face" preparations of AA, and (4) quantified elastin, collagen, and cell proteins in the media of the thoracic aorta. Results showed that enalapril and losartan similarly decrease SBP and rupture of the IEL in the AA, suggesting that enalapril inhibits the latter via a decrease in the production of angiotensin II (Ang II) and not via another effect on ACE. The decrease in IEL rupture and in SBP, as well as the modifications in the parameters of the RAS, were all dose dependent. Mibefradil had little effect on the RAS and, at the highest doses, decreased SBP to an extent similar to that for enalapril at 3 mg x kg(-1) x d(-1) but did not significantly inhibit IEL rupture. Amlodipine decreased SBP, increased plasma renin concentration, and was without effect on IEL rupture. All treatments at the highest doses had a hypotrophic effect on the aortic media but differed in their effects on the heart, with enalapril and losartan decreasing and mibefradil and amlodipine increasing heart weight, suggesting that the inhibition of IEL rupture may be related to a cardiac hypotrophic effect. All these results, taken together, suggest that Ang II plays a role in the rupture of the IEL that is, in part, independent of SBP.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Animals; Aorta, Abdominal; Aorta, Thoracic; Aortic Rupture; Benzimidazoles; Blood Pressure; Body Weight; Calcium Channel Blockers; Collagen; Elastic Tissue; Elastin; Enalapril; Heart; Heart Rate; Losartan; Male; Mibefradil; Muscle, Smooth, Vascular; Organ Size; Peptidyl-Dipeptidase A; Rats; Rats, Inbred BN; Renin; Renin-Angiotensin System; Tetrahydronaphthalenes

We investigated possible links between left ventricular mass and central arterial elasticity in the adult spontaneously hypertensive rat (SHR) and in a subgroup of SHR in which blood pressure was normalized by chronic antihypertensive drug treatment; results were compared with those of age-matched normotensive Wistar-Kyoto rats. Two indexes of arterial elasticity, based on the measurement of aortic pressure pulse wave velocity, were used. First, the slope relating carotidofemoral pulse wave velocity to blood pressure in the phenylephrine-infused pithed preparation was used as a pressure-independent index of wall elasticity. Second, to account for hypertension- and treatment-induced aortic remodeling, elastic modulus was determined from the pulse wave velocity recorded when blood pressure reached that measured in awake animals before anesthesia and pithing, together with values for wall thickness and lumen diameter evaluated by histomorphometric analysis after in situ fixation at the same pressure. In control SHR, regression analysis of variance revealed significant correlations between left ventricular mass and both wave velocity/pressure slope and elastic modulus. Chronic antihypertensive treatment normalized all three parameters. In conclusion, this new technique provides experimental evidence of a link between left ventricular mass and central arterial elasticity.

Topics: Animals; Aorta, Thoracic; Blood Pressure; Body Weight; Calcium; Elastin; Hemodynamics; Hypertension; Hypertrophy, Left Ventricular; Male; Organ Size; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vascular Capacitance

Adaptive changes in cellular and connective tissue components of the lung after chronic exposure to reduced ambient oxygen and/or pressure were studied. Four-week-old male Sprague-Dawley rats were randomly divided into five groups (n = 12 each): 1) general control, room air (GC); 2) hypobaric normoxic; 3) normobaric hypoxic; 4) hypobaric hypoxic; and 5) weight-matched control, restricted food intake (WMC; weight matched to hypobaric hypoxic animals). Lung growth (lung weight and DNA, RNA, protein, hydroxyproline, and desmosine contents) diminished in WMC compared with GC. Somatic growth decreased in hypobaric and normobaric hypoxic rats compared with GC. Lung weight; DNA, RNA, protein, hydroxyproline, and desmosine contents; and RNA/DNA, protein/DNA, and desmosine/DNA ratios increased in both hypobaric and normobaric hypoxic rats compared with WMC. Hydroxyproline and desmosine contents and the hydroxyproline/DNA ratio were significantly higher in hypobaric than normobaric hypoxic rats. Hypobaric normoxia caused a slight somatic growth reduction, but biochemical parameters of lung growth remained unaffected. In conclusion, in growing animals, despite inhibition of lung growth due to reduced food consumption, accelerated lung growth in hypobaric or normobaric hypoxia occurs by hyperplastic and hypertrophic changes. Hypobaric normoxia does not affect lung growth, but connective tissue proteins accumulate slightly more in hypobaric hypoxia than in hypoxia alone.

Topics: Animals; Atmospheric Pressure; Body Weight; Collagen; DNA; Eating; Elastin; Hematocrit; Hypoxia; Lung; Male; Proteins; Rats; Rats, Sprague-Dawley; RNA

Since Vitamin C (ascorbate, AH2) is an important airway antioxidant and is an essential component of tissue repair, and since acute (4 hr) O3 toxicity is enhanced by AH2 deficiency, we hypothesized that longer-term O3 effects might also be increased. Female Hartley guinea pigs (260-330 g) were fed either an AH2-sufficient or an AH2-deficient diet 1 week prior to exposure, and were maintained on their respective diets during 1 week of continuous exposure to O3 (0, 0.2, 0.4, and 0.8 ppm, 23 hr/day), and during 1 week postexposure recovery in clean air. The AH2-deficient diet caused lung AH2 to drop to about 30% of control in 1 week, and to below 10% by the end of exposure and recovery. Body weight gains during exposure were decreased in the 0.8 ppm O3 group, while the AH2 deficiency began to affect body weights only during recovery. O3 caused a concentration-dependent decrease in total lung capacity, vital capacity, carbon monoxide diffusing capacity, nitrogen washout, and static compliance, while increasing forced expiratory flow rates and residual or end-expiratory volume (suggestive of pulmonary gas-trapping). The lung/body weight ratio and fixed lung displacement volume were also increased in O3-exposed animals. Lung pathology consisted of mononuclear cell and neutrophil infiltration, airway as well as alveolar epithelial cell hyperplasia, and general decrease in epithelial cell cytoplasm. Thickening of the interstitium and an apparent increase in collagen staining were seen at the terminal bronchiolar regions. Some of these effects were marginally exacerbated in AH2-deficient guinea pigs. One week postexposure to air reversed all O3-induced abnormalities, irrespective of AH2 deficiency. Whole lung hydroxyproline and desmosine were not changed at any time by either O3 or AH2 deficiency. Measurement of lung prolyl hydroxylase activity suggested that AH2 deficiency as well as O3 exposure may have increased the tissue levels of this enzyme. The lack of a significant increase in toxicity with the longer-term exposure scenario suggests that AH2 has minimal influence on other compensatory mechanisms developed over time.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Collagen; Desmosine; Elastin; Female; Guinea Pigs; Hydroxyproline; Lung Diseases; Lung Volume Measurements; Organ Size; Ozone; Procollagen-Proline Dioxygenase; Respiratory Function Tests; Tissue Fixation

To investigate the role of iron, ascorbate, and fructose on copper depletion and the effect of copper depletion on neonatal lung collagen, elastin, and surfactant, female rabbits were fed a control diet [10 parts per million (ppm) copper], a basal marginal copper diet (1.5 ppm), or a basal diet containing a high concentration of iron (1,750 ppm), ascorbic acid (1%, wt/wt), or fructose (20% of carbohydrates, wt/wt) or a combination of iron, ascorbic acid, and fructose throughout gestation. Whereas 10% of neonates in the control group died in the first 24 h, 27-67% of the offspring of rabbits fed the marginal copper diet died. Birth weight was also lower for the pups of the females fed the marginal copper diets. Lungs of neonates born to females fed iron or ascorbate and marginal copper diets had low levels of copper, high proportions of acid-extractable, high-molecular-weight collagen, and low lysyl-oxidase activities, consistent with incomplete maturation of collagen. The bronchoalveolar lavage fluids of newborns whose mothers were fed marginal copper diets alone or in combination with iron and/or ascorbate had lower levels of total surfactant phospholipids than the fluids from lungs of control newborns. The lower surfactant phospholipid content of these groups could be attributed mainly to lower phosphatidylcholine and, in particular, dipalmitoylphosphatidylcholine levels. These results suggest that high maternal intakes of iron, ascorbate, or their combination in pregnancy deplete biologically available copper, which in turn induces neonatal lung abnormalities.

Topics: Animals; Animals, Newborn; Ascorbic Acid; Body Weight; Collagen; Copper; Elastin; Female; Iron; Lung; Pregnancy; Pregnancy, Animal; Protein-Lysine 6-Oxidase; Pulmonary Surfactants; Rabbits

The relationship between glycation of the aortic elastin and calcium deposits in the aorta was studied in streptozocin (STZ)-induced diabetic rats. 5-Hydroxymethylfurfural (5-HMF) which was released from aortic elastin by acid, was assayed after STZ treatment as an index of early stage glycation. The amount of released 5-HMF increased at 5 weeks and paradoxically decreased at 10 weeks after STZ treatment, though it remained higher than that of control rats. This paradoxical pattern was reproduced by the in vitro incubation of elastin with glucose and it is presumably due to further advancement of glycation reactions in diabetic rats. The level of 5-HMF did not change significantly in control rats at corresponding time points of 9, 11 and 16 weeks of age. Fluorescence of porcine pancreatic elastase I-digested elastin which served as an index of advanced glycation, increased by 1.6 times at 3 weeks and reached a maximum of 1.9-fold higher than that of control rats at 10 weeks. The calcium content of the aorta at 10 weeks in diabetic rats was significantly increased by 1.4-fold compared with control rats. This study showed that the increased elastin glycation in the aorta even at the early stage of diabetes is associated with calcium deposit in the aorta. These results are consistent with the interpretation that elastin glycation in the aorta is the potential accelerating factor for diabetic macroangiopathy.

Topics: Animals; Aorta; Blood Glucose; Body Weight; Calcium; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Elastin; Glycated Hemoglobin; Glycosylation; Male; Rats; Rats, Wistar

Topics: Animals; Body Weight; Cell Nucleus; Chick Embryo; DNA; Elastin

To test the hypothesis that effects of angiotensin converting enzyme (ACE) inhibitors upon resistance vessel structure are responsible for their ability to cause long-term reduction in blood pressure.. Stroke-prone spontaneously hypertensive (SHRSP) and Wistar-Kyoto (WKY) rats were treated with enalapril or hydralazine from 4 to 15 weeks of age. Effects upon tail-cuff blood pressure, left ventricular hypertrophy and structural indices of the superior mesenteric artery (SMA) and its resistance vessels were assessed at 11 weeks of treatment and up to 11 weeks post-treatment.. Left ventricular hypertrophy was assessed by left ventricular weight:body weight ratios. Evidence of vascular structural change was obtained from tissue weight:body weight ratios, levels of RNA, DNA and expression of alpha-actin and elastin messenger (m)RNA.. The effects of enalapril and hydralazine upon left ventricular hypertrophy in SHRSP were consistent with their respective effects upon blood pressure. Both drugs prevented the development of medial hypertrophy in SMA and resistance vessels. This was accompanied by substantial reductions in RNA:DNA ratios. Alpha-actin mRNA levels were not affected by either drug but elastin mRNA levels were reduced by both drugs. During the first 12 days post-treatment there was evidence of structural change in SMA accompanying the increases in blood pressure but importantly not in the resistance vessels.. The effects of enalapril upon left ventricular hypertrophy and mesenteric arterial hypertrophy are totally consistent with responses to blood pressure and the persistence of structural changes post-treatment does not underlie the ability of the ACE inhibitors to persistently suppress hypertension.

Topics: Animals; Blood Pressure; Body Weight; DNA; Elastin; Enalapril; Heart Ventricles; Hydralazine; Hypertension; Hypertrophy, Left Ventricular; Male; Mesenteric Artery, Superior; Organ Size; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Vascular Resistance

Weanling Sprague-Dawley rats received beta-aminopropionitrile (BAPN) and/or hypertensive treatment, namely, heminephrectomy and administration of deoxycorticosterone acetate-NaCl. The BAPN-treated rats (lathyritic rats) died of dissecting aneurysm, and the victims with hypertensive treatment was greater in number and died earlier than those without the treatment, indicating that the rise of blood pressure promoted the onset of dissecting aneurysm. The elastic architecture of the ascending aortic media was examined not only by transmission electron microscopy with tannic acid stain and/or toluidine blue O stain, but also by scanning electron microscopy after hot formic acid treatment, and the area of interlaminar elastic fibers were morphometrically analyzed by a point counting method using transmission electron microscopic photographs. In the lathyritic rats, interlaminar elastic fibers showed a significant reduction compared with the control rats, and elastic fibers tended to become round-shaped and were frequently spotted with glycosaminoglycan, which suggest a disturbance of elastogenesis. On the other hand, elastic laminae were not disrupted and smooth muscle cells were well preserved. These results suggest that the alteration of the elastic architecture causes an unstable connection between each elastic lamina, and is related to the initiation and the progression of dissecting aneurysm.

Topics: Aminopropionitrile; Animals; Aorta; Aortic Aneurysm; Aortic Dissection; Blood Pressure; Body Weight; Elastic Tissue; Elastin; Glycosaminoglycans; Hypertension; Lathyrism; Male; Rats; Rats, Inbred Strains

We have investigated the effect of enalapril, an angiotensin converting-enzyme (ACE) inhibitor, on the accumulation of ventricular and vascular collagen and elastin in young, growing rats. Beginning at either 4 or 10 wk of age, male Wistar rats were treated with enalapril for 2 or 5 wk. Enalapril treatment had no significant effect on body weight and small, generally non-significant effects on systolic and diastolic blood pressures. In contrast, young enalapril-treated animals showed a marked decrease in accumulation of total elastin and collagen in both large (aorta, renal, and carotid) and smaller (superior and large mesenteric) arteries, as well as a large reduction in total collagen in both left and right ventricles. This effect also was present but less pronounced in rats treated with enalapril beginning at 10 wk of age. These data indicate that inhibition of ACE activity during a period of rapid growth significantly reduces accumulation of vascular and ventricular connective tissue and suggests that angiotensin II may be important in normal cardiovascular development and growth.

Topics: Aging; Animals; Blood Pressure; Body Weight; Cardiovascular System; Collagen; Elastin; Enalapril; Male; Organ Size; Rats; Rats, Inbred Strains

Human pulmonary hypoplasia was studied statistically and pathologically in a large series of autopsy cases. Multiple logistic regression analysis indicated five independent risk factors from 10 statistically significant factors for pulmonary hypoplasia: (1) hydrops fetalis; (2) renal anomalies; (3) hernia, including diaphragmatic hernia and omphalocele; (4) skeletal anomalies; and (5) abnormalities of amniotic fluid, such as oligohydramnios and polyhydramnios. The characteristics of pulmonary hypoplasia for each factor were defined by morphological, morphometric, and biochemical methods. All bronchiolar branching, acinar complexity, and acinar maturation were retarded in hypoplastic lungs with hydrops fetalis, renal anomalies, affected side of diaphragmatic hernia, omphalocele, and skeletal anomalies. Only acinar complexity and maturation were impaired in the lung with oligohydramnios due to prolonged rupture of membranes. The pathogenesis of pulmonary hypoplasias should be considered differently with each associated anomaly and time of impairment. While impairment in early gestational stage before 16 weeks' gestation results in both reduced bronchiolar branching and retarded acinar development, that, at late stage, influences only acinar development.

Topics: Amino Acids; Blood-Air Barrier; Body Weight; Bronchi; Elastin; Humans; Infant, Newborn; Lung; Lung Diseases; Microscopy, Electron; Microscopy, Electron, Scanning; Organ Size; Pulmonary Alveoli

The relative contributions of the hemodynamic and morphological (vascular and cardiac) modifications induced by long-term administration of an angiotensin I-converting enzyme inhibitor, quinapril, to the drug's long-lasting preventive effects vis-à-vis genetic hypertension development (GHD) have been investigated in young spontaneously hypertensive rats (SHRs). Two groups of SHRs were given quinapril (10 mg/kg/day) or distilled water from 5 to 20 weeks of age. The drug was then stopped, but observations continued for another 7 weeks. At selected times systemic and regional hemodynamic parameters as well as cardiac and vascular morphological effects were investigated. During the treatment period, quinapril partially opposed GHD and limited the early rise in total peripheral and regional vascular resistances observed in control animals. Quinapril's partial preventive effect vis-à-vis GHD persisted, but faded after treatment withdrawal. From a morphological point of view, quinapril strongly opposed aortic wall hypertrophy as evidenced by significant reductions in media thickness and wall to lumen ratio and by a significant increase in aortic nuclear density. Quinapril also limited vascular fibrosis development. At the cardiac level, quinapril reduced heart weight to body weight ratio and opposed myocardial hypertrophy and cardiac collagen synthesis. All these vascular and cardiac morphological changes were delayed (starting after 9-15 weeks of treatment) as compared to quinapril's hemodynamic effects. Finally, the drug's vascular and cardiac antihypertrophic properties persisted after treatment withdrawal. In conclusion, our data indicate that the early systemic and regional hemodynamic effects of quinapril initiate its antihypertensive action, but the drug-induced delayed and prolonged vascular morphological changes later take over and may be partly responsible for quinapril's residual blood pressure lowering effects after treatment withdrawal.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Body Weight; Cardiac Output; Collagen; Coronary Circulation; Elastin; Enalapril; Heart; Heart Rate; Hemodynamics; Hypertension; Isoquinolines; Male; Organ Size; Quinapril; Rats; Rats, Inbred SHR; Tetrahydroisoquinolines; Ventricular Function, Left

The effects of chronic treatment of young rats (initially 8 weeks old) with the collagen cross-linking inhibitor, beta-aminoproprionitrile (BAPN), on arterial wall properties were studied. BAPN was added to the drinking water for 8 weeks to produce intakes of 0, 100, 200 and 400 mg/kg/day. Systolic pressure of treated animals did not increase with age as rapidly as that of untreated controls. Weight gain of treated animals was inhibited at the highest (BAPN) treatment level. Passive stiffness of isolated, cylindrical segments of carotid arteries was decreased in BAPN-treated animals in a dose-dependent manner. BAPN treatment had no significant effect on the total collagen or elastin content (hydroxyproline) of carotid arteries. Values of maximum active force development to 10 microM norepinephrine plus 75 mM K+ were decreased by BAPN treatment in a dose-dependent manner. There was no significant effect of BAPN treatment on total water content or its cellular and extracellular components in the carotid artery. The relative cell volume of carotid arteries was not altered by BAPN treatment, suggesting that the decreased force development was a characteristic of individual cells. These results suggest that BAPN treatment may decrease stiffness by altering secondary characteristics of the connective tissue matrix without affecting connective tissue content. The decreased maximum smooth muscle force development may be responsible for the blood pressure-lowering effects of BAPN.

Topics: Administration, Oral; Aminopropionitrile; Animals; Blood Pressure; Body Weight; Carotid Arteries; Collagen; Dose-Response Relationship, Drug; Elastin; Rats; Vasoconstriction

The ontogenesis of elastin and collagen accumulation and growth of the lung were studied in Wistar rats from day 18 of gestation until day 30 postnatally. Dexamethasone phosphate 0.1 mg or normal saline solution every 8 h for three doses was injected into pregnant rats on day 17. The effects of treatment, age, and sex on lung wet weight, lung dry weight, body weight, DNA, protein and desmosine (estimated by radioimmunoassay), and hydroxyproline were determined in the offspring. Dexamethasone inhibited lung growth and, to a lesser extent, body weight gain. While lung wet weight, lung dry weight, and body weight remained significantly reduced until postnatal day 15, the lung weight/body weight ratio was depressed only until postnatal day 5. The lung dry weight/lung wet weight ratio was decreased on day 20 of gestation and at birth. DNA concentration remained slightly but significantly reduced throughout the study period. Desmosine but not hydroxyproline concentration was lower after dexamethasone treatment during the period of rapid postnatal desmosine accumulation (day 10 p less than 0.05, day 15 p less than 0.01, day 20 p = 0.06).

Topics: Animals; Body Weight; Collagen; Desmosine; Dexamethasone; Elastin; Female; Fetus; Hydroxyproline; Lung; Male; Organ Size; Pregnancy; Rats; Rats, Inbred Strains

We studied damage and repair of lung connective tissue in rats exposed to toxic amounts of oxygen by measuring lung content of collagen and elastin and the number of collagen fragments in lung lavage fluid after exposure to 98% O2 for 60 h. Lung collagen was decreased 17%, and collagen fragments in lavage fluid were increased 4- to 5-fold in O2-exposed rats compared with those in control rats. No biochemical evidence of elastin degradation was found. Mild emphysematous changes and a leftward shift of fluid-filled, pressure-volume curves were induced within 2 wk after recovery from exposure to O2. Administration of the lathyrogen beta-aminopropionitrile worsened the emphysematous lesion produced by hyperoxia, suggesting that replacement of connective tissue during repair limits the extent of emphysema. We conclude that lung collagen is degraded and an emphysematous lesion is produced by relatively short exposure to toxic amounts of oxygen.

Topics: Aging; Aminopropionitrile; Animals; Biomechanical Phenomena; Body Weight; Bronchi; Collagen; Connective Tissue; Elastin; Emphysema; Lung; Male; Oxygen; Proteins; Pulmonary Alveoli; Rats; Rats, Inbred Strains; Therapeutic Irrigation; Wound Healing

Changes of soluble and insoluble fractions of pulmonary connective tissue proteins were studied in rats for 2-84 days following a single intratracheal instillation of cadmium chloride (10 micrograms Cd2+/lung). A transient decrease in body weight and an immediate increase in lung wet weight (200% of control value, P less than 0.01) were observed. Incorporation of [14C]proline and its conversion to [14C]hydroxyproline in vivo into different soluble and insoluble fractions of connective tissue revealed an increased metabolic turnover elicited by cadmium intoxication. A lag in the maturation of collagen into higher functional forms in the early phase of the process was demonstrated. A striking decrease in elastin was found in first 7 days (40-50%). However, this acute damage of pulmonary connective tissue was followed by a permanent increase of collagen and elastin concentration in the later phase of recovery. Histopathologic examination 14-84 days after cadmium instillation confirmed the presence of lesions in pulmonary tissue with an initial inflammation followed by reparatory changes.

Topics: Animals; Body Weight; Cadmium; Cadmium Chloride; Carbon Radioisotopes; Collagen; Connective Tissue; Elastin; Hydroxyproline; Lung; Male; Proline; Rats; Rats, Inbred Strains

Topics: Animals; Body Weight; Collagen; Elastin; Environmental Exposure; Lung; Male; Ozone; Pulmonary Emphysema; Rats; Rats, Inbred Strains

This study was done to ascertain whether hyperbaric oxygenation really affects testicular activity in rats. We evaluated serum testosterone concentration, testicular content of connective tissue protein and histological analysis of testes in each rat treated with 2 or 3 atmospheric pressures associated with oxygen saturation, together or singly for 90 minutes daily for 58 days. There were no significant differences in serum testosterone concentrations between the examined groups. The amounts of collagen, non-collagenous protein or elastin in testis were similar in all groups except one set of determinations. In addition, no prominent histological differences were noted in the testes of the animals. Thus, the pressure environment of this study, which can be regarded as almost the same as that of the hyperbaric oxygenation chamber in clinical use, appears to be nontoxic to rat testes.

Topics: Animals; Body Weight; Collagen; Elastin; Hyperbaric Oxygenation; Male; Organ Size; Oxygen; Proteins; Rats; Rats, Inbred Strains; Testis; Testosterone

This report describes an investigation of the effects of developing hypertension on the synthesis and accumulation of insoluble elastin in the thoracic aorta of young rats. Uninephrectomized male rats were made hypertensive by administration of deoxycorticosterone acetate and addition of 1% NaCl to their drinking water. Divergence of systolic blood pressures between treated and control animals and hypertrophy of the vessel began after about 2 weeks of treatment. Coincident with the appearance of hypertrophy, there was an increased accumulation of insoluble elastin in the aorta and a large increase in the capacity of the aortic tissue to synthesize elastin. However, in spite of continued increases in blood pressure and vessel hypertrophy, this effect on elastin synthesis and accumulation was transient. The results of this study suggest that synthesis of elastin in aortic tissue of young rats is highly sensitive to alterations in blood pressure.

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Blood Pressure; Body Weight; Desoxycorticosterone; DNA; Elastin; Hypertension; Male; Rats; Rats, Inbred WKY; Time Factors

Two groups of rats (young and old) were food-deprived for 3 wk and were compared with age-matched fed groups. Final body weight and dry and wet weights of lungs were significantly reduced in both young and old starved rats. As determined by saline volume-pressure (VP) curves, lungs of young starved rats accepted significantly less volume at all pressure levels compared with lungs of young fed rats. When expressed as a percent of maximum lung volume, the VP curve in young starved rats was significantly shifted upward at low lung volumes. In the old rats, the VP curves were similar in fed and starved rats. Total lung content of protein, DNA, crude connective tissue, hydroxyproline, and elastin were significantly reduced in young starved compared with young fed rats, whereas in old starved rats only protein and DNA contents were lower than those in old fed animals. It appears that in rapidly growing young rats starvation leads to growth retardation, loss of connective tissue components, and possibly reduction in tissue elastic forces at low lung volumes, whereas starvation has no significant effects on lung mechanics and connective tissue in old rats.

Topics: Age Factors; Animals; Body Weight; Connective Tissue; DNA; Elasticity; Elastin; Hydroxyproline; Lung; Lung Volume Measurements; Male; Organ Size; Proteins; Rats; Specific Pathogen-Free Organisms; Starvation; Time Factors

Groups of Fischer-344 rats were exposed to either filtered air, 0.4, 1.4, or 4.0 ppm acrolein for 62 days (6 h/day, 5 days/week). Mortality was observed only in the 4.0 ppm chamber, where 32 of 57 male rats died, but none of the 8 exposed females died. The lungs of the 4.0 ppm group were heavier than those of the larger control animals. Relative to controls, there was a 20% increase in total dry lung weight while the percent dry weight decreased 1.5% in the high dose group. This increased dry weight and the absence of significant changes in the DNA and protein content per unit dry weight indicated that the greater lung weight observed in this group was in part due to increased cellularity. Lung connective tissue content was increased as a result of subchronic acrolein exposure. The amount of elastin per unit dry weight was 173% of control values in the animals exposed to 4.0 ppm acrolein. Collagen levels were elevated in both the 1.4 and 4.0 ppm groups, 113 and 137%, respectively, of control values. Histologically, the 4.0 ppm animals demonstrated bronchiolar epithelial necrosis and sloughing, bronchiolar edema with macrophages, and focal pulmonary edema. Exposure related lesions were observed in only 3 of the 31 rats examined from the 1.4 ppm chamber and in none of the animals exposed to 0.4 ppm acrolein.

Topics: Acrolein; Aldehydes; Animals; Body Weight; Collagen; DNA; Edema; Elastin; Female; Kinetics; Lung; Lung Diseases; Male; Necrosis; Organ Size; Proteins; Rats; Rats, Inbred F344

Female rabbits on an atherogenic diet were treated with cottonseed oil (control), tamoxifen, testosterone, or progesterone. After 10 weeks the rabbits were killed, the aortas quickly removed, graded for atherosclerosis, and incubated with [14C]proline to determine collagen and elastin synthesis. Rabbits treated with testosterone and progesterone had the greatest degree of atherosclerosis, the highest DPM in hydroxyproline of collagen and elastin, and the greatest accumulation of collagen and elastin in the aorta. Tamoxifen-treated rabbits had less incorporation of radioactivity. In separate experiments aortas of similarly treated rabbits were analyzed for estradiol and progesterone receptor density. These receptors were found to be present, and progesterone and testosterone administration caused a translocation of progesterone receptors from cytosol to nucleus. Results are consistent with the hypothesis that sex hormones can affect the development of atherosclerosis through a direct effect of the hormones on arterial wall to alter collagen and elastin synthesis, the effect being mediated through hormone receptors in the wall.

Topics: Animals; Arteries; Arteriosclerosis; Body Weight; Cholesterol; Collagen; Elastin; Female; Gonadal Steroid Hormones; Progesterone; Rabbits; Receptors, Estradiol; Receptors, Progesterone; Tamoxifen; Testosterone

The static elasticity and scleroprotein content of the aorta have been measured in 24 Okamoto spontaneously hypertensive rats aged 22-25 weeks, and 24 Wistars of the same age in which hypertension had been induced by nephrectomy and treated with a steroid. From the age of 4 weeks half the animals in each group were treated with a diuretic drug. By the age of 15 weeks caudal artery systolic blood pressure was significantly lower than control values in both drug-treated groups and remained so until death. Both types of hypertension were associated with larger diameter, thicker-walled and heavier aortas than those in the drug-treated animals. Vessels from Okamoto animals contained more collagen than those from the Wistars, although the collagen content was unchanged by drug treatment. Neither drug nor strain had any clear-cut affect on elastin content. In spite of these differences in wall thickness and chemical composition, values of the functional stiffness of the aorta measured over a wide range of pressure were similar in all four groups of animals. Using a simple model of the aorta in which elastin and collagen bear stress in parallel we find that the relationship between vessel composition and static incremental elastic modulus (structural stiffness) is similar in both models of hypertension and is not changed by drug treatment in spite of the consequent reduction in blood pressure.

Topics: Aging; Animals; Aorta; Aorta, Abdominal; Aorta, Thoracic; Body Weight; Chlorthalidone; Collagen; Elasticity; Elastin; Hypertension; Male; Organ Size; Rats; Rats, Inbred Strains

Two groups of weanling or young adult rats were fed ad lib casein-based diets containing 4 or 16% protein. Food was restricted in a third group (fed the 16% protein diet) to the amount consumed daily by rats (adult or weanlings) fed the 4% diet. After 3 weeks (weanlings) or 1, 3 or 5 weeks (adults), one-half of the rats in each group were exposed to 0.64 ppm (1.28 mg/m3) of ozone for 7 days (23.5 h each day). Several parameters were then evaluated related to lung connective tissue metabolism including: (1) total lung hydroxyproline, (2) total lung elastin, (3) apparent rates for lung collagen synthesis and elastin accumulation and (4) lung and body weights. In general, the response to protein deficiency and food restriction was more pronounced than to ozone exposure. Protein deficiency and food restriction resulted in decreased lung size and collagen content. However, the ability of lung to respond to ozone (in relative terms) was not altered by changes in diet as assessed by changes in lung weight or the collagen synthetic rate.

Topics: Animals; Body Weight; Collagen; Elastin; Food Deprivation; Lung; Male; Ozone; Protein Deficiency; Rats; Rats, Inbred Strains

The chemical composition of the aorta, carotid, coronary and cerebral arteries of the cynomolgus monkey was determined during the induction and 'regression' of atherosclerosis. The feeding of a 2% cholesterol and 10% butter diet for 6 months resulted in extensive and severe atherosclerosis involving the aorta, carotid and coronary arteries. The involvement of these vessels was reflected by increases in arterial weight and chemical content of cholesterol, collagen, elastin, glycosaminoglycans (GAGs) and calcium. The cerebral arteries, which showed no atherosclerotic involvement, likewise showed no significant changes in weight and composition. During the 12-month regression period marked changes in the chemical composition of the involved arteries occurred and these included further increases in the collagen, GAG and calcium content of the vessels and decreases in the free and esterified cholesterol content. These changes were consistent with the gross and microscopic findings which revealed that during regression the pre-established lesions had not decreased in size but had become more fibrotic and calcified while the number of foam cells and amount of lipid contained in the lesion had decreased. During induction and regression, much of the cholesterol contained in the involved vessels appeared to be present in a crystalline form as indicated by the appearance of cholesterol clefts in the lesions. Aortic collagen was not altered with respect to amino acid composition and behavior in acrylamide gels throughout the study. However, elastin prepared by hot alkali treatment from diseased vessels, showed minor changes in amino acids during induction and marked changes during regression presumably due to the binding of glycoproteins to the elastin. The GAG composition of the involved arteries did not change during induction, whereas during regression the percent dermatan sulfate increased while the percent of heparan sulfate decreased. The over-all findings are consistent with the concept that the interaction of the connective tissue proteins with the GAGs, lipoproteins and calcium of the artery plays an important role in the development and regression of advanced atherosclerotic disease.

Topics: Animals; Arteries; Arteriosclerosis; Body Weight; Calcium; Cholesterol; Collagen; Connective Tissue; Coronary Vessels; Elastin; Glycosaminoglycans; Macaca fascicularis; Male

The effects of ascorbic acid supplementation on the pulmonary toxicity induced by bleomycin were examined. Swiss-Webster mice were fed an ascorbate-free diet supplemented with ascorbic acid at 0%, 0.2%, or 1.0% of the diet for 2 weeks. Bleomycin (0.15 units) was instilled intratracheally and the mice were killed 1 week later. Bleomycin caused pulmonary inflammation and edema as noted by the increases in lung wet weight and lung wet-weight-to-dry-weight ratios. The activity of prolyl hydroxylase was increased 1.4-fold to 1.6-fold in response to bleomycin, but only minor increases were observed in the collagen and elastin content of the lung. Prior dietary ascorbic acid supplementation did not reverse the effects induced by bleomycin. Interestingly, each dietary level of supplemental ascorbic acid resulted in a slight increase in the elastin and collagen content of the lung in comparison with lungs from mice consuming no ascorbic acid in their diet. The data suggest that high levels of ascorbic acid supplementation may aggravate the response to bleomycin.

Topics: Animals; Ascorbic Acid; Bleomycin; Body Weight; Collagen; Connective Tissue; Desmosine; Diet; Drug Interactions; Elastin; Hydroxyproline; Lung; Mice; Organ Size; Procollagen-Proline Dioxygenase

Adult male rats were starved by allowing them one fifth of their measured daily food consumption until they lost 40% of their initial body weights. Some of these rats were then refed until their initial body weights were reached. We measured the total content of the following in the lung tissue of fed, starved, and refed animals: (1) elastin, (2) hydroxyproline, and (3) protein. Body weight and lung dry and wet weights were significantly reduced in starved and similar in refed rats compared with fed animals. Total contents of crude connective tissue, hydroxyproline, elastin, and protein were significantly lower in starved than in fed rat lungs. After refeeding, hydroxyproline content returned completely to levels found in fed rats, but other components only partially returned to normal values. These results provide a biochemical counterpart for our previous observations on the effects of starvation and refeeding on lung mechanics and morphologic aspects. It appears that the emphysema like changes in the lungs of starved rats are at least partly related to the loss of connective tissue elements.

Topics: Animals; Body Weight; Connective Tissue; Elastin; Hydroxyproline; Lung; Male; Organ Size; Proteins; Rats; Starvation

Groups of weanling (approximately 50 g) or young adult (approximately 300 g) rats were fed ad libitum casein-based diets varying in protein content from 4 to 16%. A group was also fed the 16% protein diet in an amount on a daily basis restricted to that consumed by the protein-deficient group (4% protein). The rats were fed the diets for either 4 weeks (weanling) or 6 weeks (adults). Protein-deficient or "food-restricted" rats (whether weanling or adults) were smaller and had smaller lungs than rats fed ad libitum the diets containing 16% protein. The lung elastin content was more resistant to dietary manipulation than was the lung collagen content. Lung collagen was significantly decreased in both weanling and adult rats fed the 4% protein diet. In weanling rats, pressure-volume relationships derived from saline-filled lungs (analyzed by exponential curve-fitting methods) suggested that lungs from food-restricted rats may be less compliant than lungs from rats fed the control diet ad libitum. When expressed in absolute terms, lungs from protein-deficient rats also appeared to be less compliant than normal rats; however, on a relative basis (percentage of volume at a given recoil pressure or the expression of volume on a weight basis) differences in compliance were less apparent. It is proposed that in weanling rats the differences in lung composition and compliance are the result of retarded lung growth and perhaps development.

Topics: Age Factors; Animals; Body Weight; Caseins; Collagen; Diet; Dose-Response Relationship, Drug; Elastin; Lung; Lung Compliance; Lung Volume Measurements; Male; Protein Deficiency; Rats; Rats, Inbred Strains

Penicillamine was administered intraperitoneally to male golden hamsters for 30 days following a single intratracheal dose of bleomycin. Penicillamine treatment increased soluble collagen and decreased glycosaminoglycans in both normal and fibrotic lungs; total collagen and elastin were not significantly changed in normals but were lower in fibrotic animals. The proportions of the different glycosaminoglycans were not affected by penicillamine treatment. When related to body weight, the total lung capacity, vital capacity, and compliance both at low and high lung volumes were increased in animals that received only penicillamine when compared with animals that did not, but interpretation of these results is difficult because penicillamine-treated animals had low body weights. Lung statics were the same in animals that received penicillamine after bleomycin as in those that received bleomycin only, though penicillamine partially reversed the connective tissue expression of the bleomycin lung injury. We conclude that factors other than connective tissue levels are important in determining the mechanical behavior of fibrotic lungs.

Topics: Animals; Bleomycin; Body Weight; Collagen; Connective Tissue; Cricetinae; Elastin; Lung; Male; Mesocricetus; Penicillamine

Topics: Acetylglucosaminidase; Acid Phosphatase; Animals; Antihypertensive Agents; Aorta; Arteries; Body Weight; Collagen; Desoxycorticosterone; Elastin; Glucose-6-Phosphatase; Hexosaminidases; Hypertension; Male; Nucleotidases; Organ Size; Rats; Rats, Inbred Strains

Aortic collagen and elastin were quantitated in three groups of castrated and two groups of noncastrated male rats treated by intramuscular injection for 3 wk with oil, testosterone, or estradiol. The greatest differences were found between the castrated rats receiving testosterone and those receiving estradiol, the estradiol-treated rats having significantly lower total collagen, percent collagen, total elastin, and collagen/elastin (C/E), and higher percent elastin than those rats receiving testosterone. In noncastrated rats, administration of estradiol resulted in significantly lower total collagen, percent collagen, total elastin, and C/E. Systolic blood pressure was highest in rats receiving testerone and lowest in rats receiving estradiol. It is concluded that 1) estradiol in the presence or absence of testosterone decreases total accumulation of vascular connective tissue and alters the proportions of collagen and elastin so that the vessel is more distensible, 2) testosterone has an opposite but less marked effect than estradiol on vascular connective tissue, and 3) estradiol and testosterone alter blood pressure in opposite directions in the male rat.

Topics: Animals; Aorta; Blood Pressure; Body Weight; Castration; Collagen; Elastin; Estradiol; Male; Organ Size; Rats; Testosterone

The contributions of the relative radius, relative wall thickness, incremental strain, incremental elastic modulus, and medial scleroprotein content to the static elastic properties of the rat aortic wall have been examined in three groups of rats. Controls, rats made hypertensive at four weeks of age, and rats whose blood pressure was lowered after 6 weeks hypertension, were studied. The results show evidence of adaptive changes in the aorta of hypertensive animals, and that irreversible alterations in the mechanical properties of the wall may be induced by a brief period of hypertension. A direct relationship between aortic medial scleroprotein content and the elastic properties of the wall is demonstrated.

Topics: Age Factors; Animals; Aorta; Aorta, Abdominal; Aorta, Thoracic; Body Weight; Collagen; Elasticity; Elastin; Hypertension; Male; Nephrectomy; Organ Size; Rats

In a machine for tensile tests the ultimate strength, stress and strain of the aorta ascendens of 47 female pigs (German landrace) at three different regions of the vessel wall were determined. The animals were fattened under identical conditions in a progeny testing station and slaughtered at the same living weight (102 +/- 2 kg). Weak regressions of body weight and age on parameters measured were nevertheless accounted for. The average elastin content of the aorta ascendens diminished with advancing age but was not significantly correlated to biomechanical properties of the three single samples. Maximum load, stress and modulus of vessel wall segment I (stamped out nearer to the heart) was greater than in sample II. These circumferential segments however exhibited highly stronger biomechanical resistance than sample III, which was stamped longitudinally. In samples I and II there was a negative correlation between thickness of the wall and ultimate tensile stress (N/mm2). Freezing of the material prior to test at -18degrees C for one week resulted in a significant rise in ultimate tensile strength and stress. The meaning of these findings for comparative angiology is discussed.

Topics: Age Factors; Animals; Aorta; Biomechanical Phenomena; Body Weight; Elastin; Female; Freezing; Stress, Mechanical; Swine; Tensile Strength

Topics: Aging; Animals; Aorta; Arteries; Body Weight; Collagen; Connective Tissue; Elastin; Female; Heart; Hypertension; Male; Muscle, Smooth; Organ Size; Rats

Topics: Animals; Aorta, Thoracic; Body Weight; Carbon Radioisotopes; Collagen; Connective Tissue; Depression, Chemical; DNA; Eating; Elastin; Fasting; Glycosaminoglycans; Hydroxyproline; Male; Nitrogen; Prednisone; Proline; Rabbits; RNA; Serum Albumin, Radio-Iodinated; Skin; Sodium Chloride; Stimulation, Chemical; Sulfur Radioisotopes

Topics: Actomyosin; Aging; Animals; Aorta; Blood Pressure; Blood Proteins; Body Weight; Carbon Radioisotopes; Elastin; Hypertension; Kinetics; Liver; Lysine; Male; Myocardium; Organ Size; Rats; Rats, Inbred Strains; Time Factors

Topics: Androgen Antagonists; Androstanes; Animals; Aorta, Thoracic; Blood Pressure; Body Weight; Castration; Collagen; Cyproterone; Elastin; Hypertension; Male; Muscle, Smooth; Organ Size; Proteins; Rats

Topics: Animals; Aorta; Aorta, Thoracic; Arteriosclerosis; Body Weight; Castration; Collagen; DNA; Elastin; Estradiol; Estrogens; Female; Menopause; Organ Size; Ovary; Proteins; Rats; Uterus

Topics: Age Factors; Animals; Aorta; Aorta, Abdominal; Aorta, Thoracic; Autoradiography; Biometry; Body Weight; Cell Division; Elastic Tissue; Elastin; Epithelium; Female; Histocytochemistry; Male; Muscle, Smooth; Rats; Sex Factors; Tritium

Topics: Aldehydes; Amino Acid Oxidoreductases; Amino Acids; Ammonium Sulfate; Animals; Aorta; Body Weight; Chickens; Chromatography, Gel; Collagen; Copper; Deficiency Diseases; Elastin; Electrophoresis, Disc; Formates; Lysine; Monoamine Oxidase; Solubility; Tendons

Topics: Animals; Aorta; Body Weight; Carbon Isotopes; Castration; Collagen; Elastin; Estradiol; Female; Hydroxyproline; Ovary; Proline; Rats; Stimulation, Chemical

Topics: Aminopropionitrile; Animals; Aorta, Abdominal; Arteries; Body Weight; Collagen; Disease Models, Animal; Edema; Elastin; Female; Ferrocyanides; Haplorhini; Hemorrhage; Hemosiderosis; Iliac Artery; Lathyrism; Macaca; Male; Sternum; Thoracic Arteries

Topics: Amino Acids; Animals; Aorta, Thoracic; Aortic Diseases; Blood Pressure; Body Weight; Collagen; Dilatation; Elastin; Female; Heart; Hypertension; Male; Organ Size; Proteins; Rats; Sex Factors

Topics: Aging; Animals; Body Weight; Elastin; Female; Humans; Male; Organ Size; Pancreas; Rats; Rats, Inbred Strains; Sex Factors

Topics: Amino Acids; Animals; Autoradiography; Basement Membrane; Body Weight; Carbon Isotopes; Chromatography, Thin Layer; Collagen; Cricetinae; Elastin; Endoplasmic Reticulum; Erythrocytes; Female; Hemopneumothorax; Male; Microscopy, Electron; Papain; Phosphatidylcholines; Pleura; Protein Biosynthesis; Pulmonary Alveoli; Pulmonary Edema; Pulmonary Emphysema; Time Factors

Topics: Age Factors; Animals; Animals, Newborn; Aorta; Body Weight; Elastin; Glucocorticoids; Hydrocortisone; Rats; Triamcinolone

Topics: Animals; Aorta; Aorta, Thoracic; Arteriosclerosis; Blood Pressure; Body Weight; Collagen; Desoxycorticosterone; Elasticity; Elastin; Hypertension; Male; Organ Size; Rats

Topics: Age Factors; Aging; Animals; Body Weight; Collagen; Elastin; Foot; Hypertrophy; Muscle Denervation; Muscles; Organ Size; Rats

Topics: Aging; Animal Feed; Animals; Aorta; Body Weight; Connective Tissue; Elastin; Female; Hexosamines; Hydroxyproline; Proteins; Swine; Uterus

Topics: Anatomy, Comparative; Animals; Aorta; Aorta, Abdominal; Aorta, Thoracic; Arteriosclerosis; Body Weight; Cats; Cattle; Collagen; Dogs; Elastin; Hemodynamics; Horses; Mice; Pressure; Rabbits; Rats; Sheep; Species Specificity; Swine; Vasa Vasorum

Topics: Adult; Age Factors; Body Weight; Chemical Phenomena; Chemistry; Child; Child, Preschool; Collagen; Elastin; Histocytochemistry; Humans; Infant; Infant, Newborn; Kidney; Microscopy, Fluorescence; Microscopy, Polarization; Resorcinols; Rosaniline Dyes; Staining and Labeling; X-Ray Diffraction

Topics: Animals; Aorta; Arteriosclerosis; Body Weight; Cholesterol; Collagen; Elastin; Lipids; Liver; Lung; Male; Myocardium; Peptide Hydrolases; Phospholipids; Rabbits