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Cardiovascular System (cardiovascular + system)
Selected AbstractsENDOTHELINS AND NADPH OXIDASES IN THE CARDIOVASCULAR SYSTEMCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1 2008Karigowda J Dammanahalli SUMMARY 1The endothelin (ET) system and NADPH oxidase play important roles in the regulation of cardiovascular function, as well as in the pathogenesis of hypertension and other cardiovascular diseases. 2Endothelins activate NADPH oxidases and thereby increase superoxide production, resulting in oxidative stress and cardiovascular dysfunction. Thus, NADPH oxidases may mediate the role of endothelins in some cardiovascular diseases. However, the role of reactive oxygen species (ROS) in mediating ET-induced vasoconstriction and cardiovascular disease remains under debate, as evidenced by conflicting reports from different research teams. Conversely, activation of NADPH oxidase can stimulate ET secretion via ROS generation, which further enhances the cardiovascular effects of NADPH oxidase. However, little is known about how ROS activate the endothelin system. It seems that the relationship between ET-1 and ROS may vary with cardiovascular disorders. 3Endothelins activate NADPH oxidase via the ET receptor,proline-rich tyrosine kinase-2 (Pyk2),Rac1 pathway. Rac1 is an important regulator of NADPH oxidase. There is ample evidence supporting direct stimulation by Rac1 of NADPH oxidase activity. In addition, Rac1-induced cardiomyocyte hypertrophy is mediated by the generation of ROS. [source] 5-HYDROXYTRYPTAMINE IN THE CARDIOVASCULAR SYSTEM: FOCUS ON THE SEROTONIN TRANSPORTER (SERT)CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2006Wei Ni SUMMARY 1The function of the serotonin transporter (SERT) is to take up and release serotonin (5-hydroxytyptamine (5-HT)) from cells and this function of SERT in the central nervous system (CNS) is well-documented; SERT is the target of selective serotonin reuptake inhibitors used in the treatment of CNS disorders, such as depression. 2The aim of the present review is to discuss our current knowledge of 5-HT and SERT in the cardiovascular (CV) system, as well as their function in physiological and pathophysiological states. 3The SERT protein has been located in multiple CV tissues, including the heart, blood vessels, brain, platelets, adrenal gland and kidney. Modification of SERT function occurs at both transcriptional and translational levels. The functions of SERT in these tissues is largely unexplored, but includes modulation of cardiac and smooth muscle contractility, platelet aggregation, cellular mitogenesis, modulating neuronal activity and urinary excretion. 4Recent studies have uncovered potential relationships between the expression of SERT gene promoter variants (long (l) or short (s)) with CV diseases. Specifically, the risk of myocardial infarction and pulmonary hypertension is increased with expression of the ll promoter, a variant associated with increased expression and function of SERT. The relationship between promoter variants and other CV diseases has not been investigated. 5Newly available experimental tools, such as pharmacological compounds and genetically altered mice, should prove useful in the investigation of the function of SERT in the CV system. 6In summary, the function of SERT in the CV system is just beginning to be revealed. [source] A New Pulsatile Volumetric Device With Biomorphic Valves for the In Vitro Study of the Cardiovascular SystemARTIFICIAL ORGANS, Issue 12 2009Ettore Lanzarone Abstract A pulsatile mock loop system was designed and tested. This prototype represents a versatile, adjustable, and controllable experimental apparatus for in vitro studies of devices meant to interface with the human circulatory system. The pumping system consisted of a ventricular chamber featuring two biomorphic silicone valves as the inlet and outlet valves. The chamber volume is forced by a piston pump moved by a computer-controlled, low-inertia motor. Fluid dynamic tests with the device were performed to simulate physiological conditions in terms of cardiac output (mean flow of 5 and 6 L/min, with beat rates from 60 to 80 bpm), of rheological properties of the processed fluid, and of systemic circulation impedance. The pulsating actuator performed a good replication of the physiological ventricular behavior and was able to guarantee easy control of the waveform parameters. Experimental pressure and flow tracings reliably simulated the physiological profiles, and no hemolytic subatmospheric pressures were revealed. The performance of the prototype valves was also studied in terms of dynamic and static backflow, effective orifice area, and pressure loss, resulting in their applicability for this device. Mechanical reliability was also tested over 8 h. The device proved to be a reliable lab apparatus for in vitro tests; the pumping system also represents a first step toward a possible future application of pulsating perfusion in the clinic arena, such as in short-term cardiac assist and pulsatile cardiopulmonary bypass. [source] Effects of Formaldehyde on Cardiovascular System in In Situ Rat HeartsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2009Daisuke Takeshita After 20,30 min. of intravenous infusion of 3.7% formaldehyde solution (FA) at 10 ,l (3.7 mg)/kg/min, normal and hypertrophic hearts showed significant decreases in left ventricle end-systolic pressure (ESP), heart rate and cardiac output per minute, indicating an acute pumping failure. Hypertrophic hearts showed significantly smaller ESP, stroke volumes and cardiac output than those in normal hearts. Systolic pressure,volume area at midrange left ventricular volume (PVAmLVV: a mechanical work capability index) was significantly smaller than that in normal hearts and per cent of mean PVAmLVVversus pre-infusion mean value in hypertrophic hearts was significantly decreased compared to normal hearts 30 min. after FA infusion. The marked decrease in pH, base excess and no changes in PaO2 and PaCO2 suggest metabolic acidosis. The correction of metabolic acidosis with 9% NaHCO3 did not influence on the acute pumping failure, indicating that metabolic acidosis did not cause it. Ultrastructural observations revealed marked dilation of the sarcoplasmic reticulum with intact sarcolemmal membranes and no disintegration of muscle myofibrils. Ryanodine receptors and calcium (Ca2+) pumps (SERCA2A) located in the sarcoplasmic reticulum have major roles in the cytosolic Ca2+ handling. Taken together, acute pumping failure by FA may derive from the impairment of Ca2+ handling in the cardiac excitation,contraction coupling. [source] Price development in important anesthesia and critical care medicine journals in comparison to journals of other disciplinesACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2001J. Boldt Background: In today's climate of financial restrictions, libraries and individual subscribers complain about the price increase of scientific journals. The development in prices of anesthesia/critical care journals was analysed over the past 6 years and compared to prices of some journals of other disciplines. Methods: Important journals in the categories Anesthesiology, Emergency Medicine & Critical Care, Surgery, Medicine (General), and Cardiac & Cardiovascular Systems listed in the 1999 Science Citation Index of Journal Citation Report were included and prices for the years 1995 to 2000 were analysed. Results: Increase in prices ranged from +13% to +199%. The mean increase in journal prices was lowest in the category Anesthesiology (+61%), higher in the category Critical Care (+73%), and highest in the category Medicine, General (+101%). Changes in the impact factor (IF) varied widely, ranging from a decrease (Lancet: ,43%; J Neurosurg Anesth: ,44%) to a tremendous increase (e.g. Reg Anesth +165%; Ann Emerg Med +149%). The journals' size (number of articles or pages) did not increase proportionally with the increase in prices. Conclusion: A disproportionate rise in journal prices was seen over the past 6 years. The large increase in cost may have multiple reasons. The rapidly increasing cost of research journals may affect research quality because economic pressure may result in reduction in availibility of information due to cancellation of subscriptions to journals. [source] Pulse Conductance and Flow-induced Hemolysis During Pulsatile Cardiopulmonary BypassARTIFICIAL ORGANS, Issue 4 2010Antoine P. Simons Abstract In this study, the hypothesis was tested that a low-resistant, high-compliant oxygenator provides better pulse conductance and less hemolysis than a high-resistant, low-compliant oxygenator during pulsatile cardiopulmonary bypass. Forty adults undergoing coronary artery bypass surgery were randomly divided into two groups using either an oxygenator with a relatively low hydraulic resistance (Quadrox BE-HMO 2000, Maquet Cardiopulmonary AG, Hirrlingen, Germany) or with a relatively high hydraulic resistance (Capiox SX18, Terumo Cardiovascular Systems, Tokyo, Japan). The phase shift between the flow signals measured at the inlet and outlet of the oxygenator was used to assess compliance. Pulse conductance in terms of pressure attenuation was calculated by dividing the outlet pulse pressure of the oxygenator by the inlet pulse pressure. A normalized index was used to assess hemolysis. The phase shifts in time of the flow pulses were 36 ± 6 ms in the low-resistant (high-compliant) oxygenator, and 14 ± 2 ms in the high-resistant (low-compliant) oxygenator group (P < 0.001). The low-resistant, high-compliant oxygenator provided 27% better pulse conductance compared with the high-resistant, low-compliant oxygenator (0.84 ± 0.02 and 0.66 ± 0.01, respectively, P < 0.001). Inlet pulse pressures were significantly higher (29%) in the high-resistant, low-compliant (Capiox) group than in the low-resistant, high-compliant (Quadrox) group (838 ± 38 mm Hg and 648 ± 25 mm Hg respectively, P < 0.001), but no significant difference in hemolysis was found. A low-resistant, high-compliant oxygenator provides better pulse conduction than a high-resistant, low-compliant oxygenator. However, the study data could not confirm the association of high pressures with increased hemolysis. [source] REVIEW: Role of adipokines in obesity-associated hypertensionACTA PHYSIOLOGICA, Issue 2 2010M. Vlasova Abstract It has been well documented that obesity is a major risk factor for the development of the hypertensive state. The correlation between body mass index and blood pressure level is well established. Nevertheless, the exact mechanisms which contribute to obesity-related hypertension remain poorly understood. In the last years, we have realized that the white adipose tissue is not just an inert organ for nutrient storage and isolation but rather depending on the body mass index the biggest endocrinological organ. Thus, the possible contribution of adipokines to the blood pressure elevation becomes an attractive hypothesis to explain the hypertensive state that often occurs in obesity. In this review, we consider direct and indirect effects of main adipokines on structural and functional changes in the cardiovascular system. [source] Practical Assessment of Maternal Cardiovascular Risk in PregnancyCONGENITAL HEART DISEASE, Issue 5 2008Nazanin Moghbeli MD ABSTRACT Cardiovascular disease in pregnancy is the most common cause of maternal mortality in the developed world and an important cause of heart failure, stroke, and arrhythmia. As more children with congenital heart disease survive into adulthood, there is a more pressing need to understand the risks that pregnancy poses for these women. Pregnancy, labor, and delivery increase the hemodynamic stress on the cardiovascular system and place women with heart disease at increased risk of cardiovascular complications, which include heart failure and death. Systematic assessment of pregnancy risk in these women, ideally before conception, is essential in optimizing maternal and fetal outcomes. This article describes the process of assessing risk of pregnancy-associated cardiovascular complications in women with structural heart disease. We review the current literature on pregnancy risk in women with complex congenital lesions, valvular heart disease, cardiomyopathy, and aortopathy, and suggest an approach to risk stratification. Based on a review of the literature, we report features that pose an increased risk of adverse maternal and fetal outcomes, which include poor maternal functional status; prior history of heart failure, arrhythmia, or cerebral vascular events; cyanosis; poor systemic ventricular function; and severe aortic or mitral stenosis. Pulmonary hypertension and Eisenmenger syndrome place women at exceedingly high risk for cardiovascular complications in pregnancy, including maternal and fetal death. [source] The effects of acute and chronic exercise on the vasculatureACTA PHYSIOLOGICA, Issue 4 2010J. J. Whyte Abstract Regular physical activity (endurance training, ET) has a strong positive link with cardiovascular health. The aim of this review is to draw together the current knowledge on gene expression in different cell types comprising the vessels of the circulatory system, with special emphasis on the endothelium, and how these gene products interact to influence vascular health. The effect beneficial effects of ET on the endothelium are believed to result from increased vascular shear stress during ET bouts. A number of mechanosensory mechanisms have been elucidated that may contribute to the effects of ET on vascular function, but there are questions regarding interactions among molecular pathways. For instance, increases in flow brought on by ET can reduce circulating levels of viscosity and haemostatic and inflammatory variables that may interact with increased shear stress, releasing vasoactive substances such as nitric oxide and prostacyclin, decreasing permeability to plasma lipoproteins as well as the adhesion of leucocytes. At this time the optimal rate-of-flow and rate-of-change in flow for determining whether anti-atherogenic or pro-atherogenic processes proceed remain unknown. In addition, the impact of haemodynamic variables differs with vessel size and tissue type in which arteries are located. While the hurdles to understanding the mechanism responsible for ET-induced alterations in vascular cell gene expression are significant, they in no way undermine the established benefits of regular physical activity to the cardiovascular system and to general overall health. This review summarizes current understanding of control of vascular cell gene expression by exercise and how these processes lead to improved cardiovascular health. [source] Role of ß Blockers in Congestive Heart FailureCONGESTIVE HEART FAILURE, Issue 6 2000MPhil, Nazim Uddin Azam Khan MD Prolonged activation of the adrenergic nervous system has adverse consequences on the cardiovascular system in patients with congestive heart failure. , adrenergic receptor,blocker therapy modifies these deleterious effects. , blockers have been shown to improve myocardial function and survival when used in conjunction with conventional treatment with diuretics, angiotensinconverting enzyme inhibitors, and digoxin. , blocker therapy in mild-to-moderate heart failure should not be delayed because it causes some reversal of both neurohormonal compensatory mechanisms and the deletorious myocardial remodeling process. This paper reviews the beneficial effects of , adrenergic receptor-blocker therapy on the pathophysiology, symptoms, left ventricular function, morbidity, and mortality in patients with congestive heart failure. [source] The role of caveolin-1 in cardiovascular regulationACTA PHYSIOLOGICA, Issue 2 2009A. Rahman Abstract Caveolae are omega-shaped membrane invaginations present in essentially all cell types in the cardiovascular system, and numerous functions have been ascribed to these structures. Caveolae formation depends on caveolins, cholesterol and polymerase I and transcript release factor-Cavin (PTRF-Cavin). The current review summarizes and critically discusses the cardiovascular phenotypes reported in caveolin-1-deficient mice. Major changes in the structure and function of heart, lung and blood vessels have been documented, suggesting that caveolae play a critical role at the interface between blood and surrounding tissue. According to an emerging paradigm, many of these changes are secondary to uncoupling of endothelial nitric oxide synthase. Thus, nitric oxide synthase not only synthesizes more nitric oxide in the absence of caveolin-1, but also more superoxide with potential pathogenic consequences. It is further argued that the vasodilating drive from increased nitric oxide production in caveolin-1-deficient mice is balanced by changes in the vascular media that favour increased dynamic resistance regulation. Harnessing the therapeutic opportunities buried in caveolae, while challenging, could expand the arsenal of treatment options in cancer, lung disease and atherosclerosis. [source] Vitamin D and innate immunityDERMATOLOGIC THERAPY, Issue 1 2010Jeremiah Miller ABSTRACT Vitamin D's role in bone health has been well established. Recently, studies have identified additional roles of vitamin D in the immune system, cardiovascular system, and cancer prevention. The effect of vitamin D on the immune system is particularly relevant to the dermatologist in that it has implications for atopic dermatitis, psoriasis, and skin cancer. However, there is much disagreement on a dose of vitamin D that is both safe and effective as both ultraviolet exposure and certain vitamin D-rich foods come with unwanted consequences. This review aims to update the dermatologist on the roles of vitamin D in the immune system, the safety and dose of different sources, and risk factors for vitamin D deficiency that may necessitate supplementation. Immune consequences of vitamin D status represent one additional aspect that illustrates how guidelines for supplementation are needed and will only be useful clinically if they are presented in context with validated controlled clinical trials. [source] Retinoic acid is a negative physiological regulator of N-cadherin during early avian heart morphogenesisDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 9 2009Mahmoud Romeih The vitamin A-deficient (VAD) early avian embryo has a grossly abnormal cardiovascular system that is rescued by treating the embryo with the vitamin A-active form, retinoic acid (RA). Here we examine the role of N-cadherin (N-cad) in RA-regulated early cardiovascular morphogenesis. N-cad mRNA and protein are expressed globally in the presomite through HH14 normal and VAD quail embryos. The expression in VAD embryos prior to HH10 is significantly higher than that in normal embryos. Functional analyses of the N-cad overproducing VAD embryos reveal N-cad involvement in the RA-regulated cardiovascular development and suggest that N-cad expression may be mediated by Msx1. We provide evidence that in the early avian embryo, endogenous RA is a negative physiological regulator of N-cad. We hypothesize that a critical endogenous level of N-cad is needed for normal early cardiovascular morphogenesis to occur and that this level is ensured by stage-specific, developmentally regulated RA signaling. [source] Abnormal venous and arterial patterning in chordin mutantsDEVELOPMENTAL DYNAMICS, Issue 9 2007Emmanučle C. Délot Abstract Classic dye injection methods yielded amazingly detailed images of normal and pathological development of the cardiovascular system. However, because these methods rely on the beating heart of diffuse the dyes, the vessels visualized have been limited to the arterial tree, and our knowledge of vein development is lagging. In order to solve this problem, we injected pigmented methylsalicylate resins in mouse embryos after they were fixed and made transparent. This new technique allowed us to image the venous system and prompted the discovery of multiple venous anomalies in Chord,/, mutant mice. Genetic inactivation of Chordin, an inhibitor of the Bone Morphogenetic Protein signaling pathway, results in neural crest defects affecting heart and neck organs, as seen in DiGeorge syndrome patients. Injection into the descending aorta of Chrd,/, mutants demonstrated how a very severe early phenotype of the aortic arches develops into persistent truncus arteriosus. In addition, injection into the atrium revealed several patterning defects of the anterior cardinal veins and their tributaries, including absence of segments, looping and midline defects. The signals that govern the development of the individual cephalic veins are unknown, but our results show that the Bone Morphogenetic Protein pathway is necessary for the process. Developmental Dynamics 236:2586,2593, 2007. © 2007 Wiley-Liss, Inc. [source] MAP kinase activation in avian cardiovascular developmentDEVELOPMENTAL DYNAMICS, Issue 4 2004Christine M. Liberatore Abstract Signaling pathways mediated by receptor tyrosine kinases (RTK) and mitogen-activated protein kinase (MAPK) activation have multiple functions in the developing cardiovascular system. The localization of diphosphorylated extracellular signal regulated kinase (dp-ERK) was monitored as an indicator of MAPK activation in the forming heart and vasculature of avian embryos. Sustained dp-ERK expression was observed in vascular endothelial cells of embryonic and extraembryonic origins. Although dp-ERK was not detected during early cardiac lineage induction, MAPK activation was observed in the epicardial, endocardial, and myocardial compartments during heart chamber formation. Endocardial expression of dp-ERK in the valve primordia and heart chambers may reflect differential cell growth associated with RTK signaling in the heart. dp-ERK localization in the epicardium, subepicardial fibroblasts, myocardial fibroblasts, and coronary vessels is consistent with MAPK activation in epicardial-derived cell lineages. The complex temporal,spatial regulation of dp-ERK in the heart supports diverse regulatory functions for RTK signaling in different cell populations, including the endocardium, myocardium, and epicardial-derived cells during cardiac organogenesis. Developmental Dynamics 230:773,780, 2004. © 2004 Wiley-Liss, Inc. [source] Potential manipulation of endothelial progenitor cells in diabetes and its complicationsDIABETES OBESITY & METABOLISM, Issue 7 2010G. P. Fadini Diabetes mellitus increases cardiovascular risk through its negative impact on vascular endothelium. Although glucotoxicity and lipotoxicity account for endothelial cell damage, endothelial repair is also affected by diabetes. Endothelial progenitor cells (EPCs) are involved in the maintenance of endothelial homoeostasis and in the process of new vessel formation. For these reasons, EPCs are thought to have a protective impact within the cardiovascular system. In addition, EPCs appear to modulate the functioning of other organs, providing neurotropic signals and promoting repair of the glomerular endothelium. The exact mechanisms by which EPCs provide cardiovascular protection are unknown and the definition of EPCs is not standardized. Notwithstanding these limitations, the literature consistently indicates that EPCs are altered in type 1 and type 2 diabetes and in virtually all diabetic complications. Moreover, experimental models suggest that EPC-based therapies might help prevent or reverse the features of end-organ complications. This identifies EPCs as having a novel pathogenic role in diabetes and being a potential therapeutic target. Several ways of favourably modulating EPCs have been identified, including lifestyle intervention, commonly used medications and cell-based approaches. Herein, we provide a comprehensive overview of EPC pathophysiology and the potential for EPC modulation in diabetes. [source] Cardiovascular metabolic syndrome , an interplay of, obesity, inflammation, diabetes and coronary heart diseaseDIABETES OBESITY & METABOLISM, Issue 3 2007J. S. Rana Cardiovascular disease is currently one of the biggest causes of morbidity and mortality facing humanity. Such a paradigm shift of disease pattern over the last century has only worsened due to the alarming global prevalence of obesity and type 2 diabetes. In recent years there is increasing focus on inflammation as one of the key players in the patho-physiology of these disorders. In addition to these overt risk factors new research is unraveling the significance of a constellation of early metabolic abnormalities that include weight gain, insulin resistance, prehypertension and a specific pattern of dyslipidaemia. There exists a complex interrelationship of these various metabolic disorders and their effect on cardiovascular system. Simplified explanation can be that inflammation increases insulin resistance, which in turn leads to obesity while perpetuating diabetes, high blood pressure, prothrombotic state and dyslipidaemia. While inflammation and insulin resistance have direct adverse effects on cardiac muscle, these metabolic abnormalities as a whole cause causes cardiovascular complications; warranting a multi pronged therapeutic and preventive approach for the ,Cardiovascular Metabolic Syndrome' as an entity. [source] Effects of oestrogen receptor-active compounds on lipid metabolismDIABETES OBESITY & METABOLISM, Issue 5 2005Susan G. Lakoski Abstract:, Selective estrogen receptor modulators (SERMs) have been used successfully in the treatment of breast cancer and osteoporosis while Tibolone has been used extensively in Europe for the treatment of menopausal symptoms. Limited data is available on the effect of these agents on the cardiovascular system. Traditional and novel lipid markers are valuable in determining patients at increased cardiovascular risk. The purpose of this article is to discuss the mechanism of action of Tamoxifen, Raloxifene and Tibolone and their effects on lipid metabolism. [source] The pharmacology of cilostazolDIABETES OBESITY & METABOLISM, Issue 2002Karsten Schrör Cilostazol (6-[4-(1-cyclohexyl- 1H -tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quinolinone; OPC-13013) is a 2-oxo-quinoline derivative with antithrombotic, vasodilator, antimitogenic and cardiotonic properties. The compound is a potent inhibitor of phosphodiesterase (PDE) 3A, the isoform of PDE 3 in the cardiovascular system (IC50: 0.2 µm). In addition, there is inhibition of adenosine uptake, eventually resulting in changes in cAMP levels, dependent on the type of adenosine receptors (A1 or A2). Cilostazol inhibits platelet aggregation and has considerable antithrombotic effects in vivo. The compound relaxes vascular smooth muscle and inhibits mitogenesis and migration of vascular smooth muscle cells. In the heart, cilostazol causes positive inotropic and chronotropic effects. Most, if not all, of these actions are cAMP-mediated, including the modification of cAMP-controlled gene expression. Cilostazol decreases levels of serum triglycerides and causes some increase in HDL-cholesterol levels. The compound has a number of additional effects which might contribute to its overall clinical efficacy. Cilostazol undergoes intensive and finally complete hepatic metabolism via the cytochrome P450 systems. This might result in some drug interaction, i.e. with erythromycin and omeprazole. The half-life is approximately 10 h, resulting in about 2-fold accumulation of the drug during repeated administration. [source] Inflamed adipose tissue, insulin resistance and vascular injuryDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 8 2008Christian X. Andersson Abstract Type 2 diabetes is the most common metabolic disorder today and has reached epidemic proportions in many countries. Insulin resistance and inflammation play a central role in the pathogenesis of type 2 diabetes and are present long before the onset of the disease. During this time, many of the complications associated with type 2 diabetes are initiated. Of major concern is the two- to fourfold increase in cardiovascular morbidity and mortality in this group compared to a nondiabetic population. Obesity, characterized by enlarged fat cells, and insulin resistance are, like type 2 diabetes, associated with impaired adipogenesis and a low-grade chronic inflammation that to a large extent emanates from the adipose tissue. Both these processes contribute to unfavourable alterations of the circulating levels of several bioactive molecules (adipokines) that are secreted from the adipose tissue, many of which have documented inhibitory effects on insulin sensitivity in the liver and peripheral tissues and, in addition, have negative effects on the cardiovascular system. Here we review current knowledge of the adipose tissue as an endocrine organ, the local and systemic effects of a chronic state of low-grade inflammation residing in the adipose tissue, and, in particular, the effects of inflammation and circulating adipokines on the vascular wall. Copyright © 2008 John Wiley & Sons, Ltd. [source] Beneficial effects of aminoguanidine on the cardiovascular system of diabetic ratsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2005Krisztián Stadler Abstract Background The study focused on investigating the effect of aminoguanidine on cardiovascular damages in diabetes and the possible mechanisms of its action. Methods Aminoguanidine (AMNG) was used to treat streptozotocin-induced diabetic rats, and the effects were compared to those obtained under insulin treatment. Blood metabolic parameters, ,NO and ONOO, as well as protein carbonyl levels and cardiac hypertrophy were determined. Results Diabetic animals showed increased ,NO levels and markedly increased ONOO, generation in the aorta, along with a significant hypertrophy and protein carbonylation in the cardiac tissue. Both AMNG and insulin treatment suppressed the levels of overproduced ,NO or ONOO, in the vasculature, but only AMNG was able to prevent hypertrophic alterations and reduce protein carbonylation in the cardiac tissue. Conclusions Oxidative protein modification, together with cardiac hypertrophy and high generation of ,NO and ONOO,, are important early events in the development of cardiovascular complications in diabetes. Aminoguanidine could prevent hypertrophy through inhibition of production of nonenzymatic glycation products rather than via inhibition of ,NO production. Copyright © 2004 John Wiley & Sons, Ltd. [source] Diabetes mellitus and alcoholDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2004Albert van de Wiel Abstract Alcohol influences glucose metabolism in several ways in diabetic patients as well as in non-diabetic patients. Since alcohol inhibits both gluconeogenesis and glycogenolysis, its acute intake without food may provoke hypoglycaemia, especially in cases of depleted glycogen stores and in combination with sulphonylurea. Consumed with a meal including carbohydrates, it is the preferred fuel, which may initially lead to somewhat higher blood glucose levels and hence an insulin response in type 2 diabetic patients. Depending on the nature of the carbohydrates in the meal, this may be followed by reactive hypoglycaemia. Moderate consumption of alcohol is associated with a reduced risk of atherosclerotic disorders. Diabetic patients benefit from this favourable effect as much as non-diabetic patients. Apart from effects on lipid metabolism, haemostatic balance and blood pressure, alcohol improves insulin sensitivity. This improvement of insulin sensitivity may also be responsible for the lower incidence of type 2 diabetes mellitus reported to be associated with light-to-moderate drinking. In case of moderate and sensible use, risks of disturbances in glycaemic control, weight and blood pressure are limited. Excessive intake of alcohol, however, may not only cause loss of metabolic control, but also annihilate the favourable effects on the cardiovascular system. Copyright © 2004 John Wiley & Sons, Ltd. [source] Ventricular PKC-, and humoral signaling in DOCA-Salt rats treated with labedipinedilol-ADRUG DEVELOPMENT RESEARCH, Issue 3 2003Jwu-Lai Yeh Abstract Effects of oral antihypertensive monotherapy with labedipinedilol-A, labetalol, atenolol, amlodipine, prazosin (20 mg kg,1 day,1), and short-acting nifedipine (3 mg kg,1 day,1) on DOCA-salt-induced translocation of ventricular protein kinase C-,(PKC-,), humoral signaling, and the cardiovascular system were investigated in rats for 4 weeks. The triple blocking activities of labedipinedilol-A (,/,-adrenoceptor blockade and calcium entry blockade) were compared with single blocking activities of selective drugs. Cytosolic PKC-, immunoreactivity was decreased by labedipinedilol-A, short-acting nifedipine, amlodipine, prazosin, labetalol, atenolol, and losartan. Membranous PKC-, immunoreactivity was significantly decreased by labedipinedilol-A, amlodipine, prazosin, labetalol, and atenolol. Labedipinedilol-A and prazosin more potently decreased membranous than cytosolic PKC-, expression. Labedipinedilol-A, labetalol, and atenolol effectively inhibited DOCA-salt-induced increases in angiotensin II (Ang II). All antihypertensive agents reduced endothelin-1 (ET-1) levels in urine and cardiac weight growth. Treatments with labedipinedilol-A, labetalol, atenolol, and amlodipine normalized DOCA-salt-induced ANP increases. Prazosin did not decrease ANP. Short-acting nifedipine elevated ANP. During long-term antihypertensive therapy in DOCA-salt hypertensive rats, single blockade drugs did not fully inhibit ventricular PKC-, translocation or Ang II, ET-1, and ANP humoral signaling. However, triple blockade labedipinedilol-A therapy had a wide range of ,/,-adrenergic receptor and calcium channel inhibitory activities, including diminished reflux tachycardia, inhibition of PKC-, translocation, and reduction of Ang II, ET-1, and ANP formation. Drug Dev. Res. 59:307,315, 2003. 2003 Wiley-Liss, Inc. [source] Fetal Mouse Imaging Using Echocardiography: A Review of Current TechnologyECHOCARDIOGRAPHY, Issue 10 2006Christopher F. Spurney M.D. Advances in genetic research have led to the need for phenotypic analysis of small animal models. However, often these genetic alterations, especially when affecting the cardiovascular system, can result in fetal or perinatal death. Noninvasive ultrasound imaging is an ideal method for detecting and studying such congenital malformations, as it allows early recognition of abnormalities in the living fetus and the progression of disease can be followed in utero with longitudinal studies. Two platforms for fetal mouse echocardiography exist, the clinical systems with 15-MHz phased array transducers and research systems with 20,55-MHz mechanical transducers. The clinical ultrasound system has limited two-dimensional (2D) resolution (axial resolution of 440 ,m), but the availability of color and spectral Doppler allows quick interrogations of blood flows, facilitating the detection of structural abnormalities. M-mode imaging further provides important functional data, although, the proper imaging planes are often difficult to obtain. In comparison, the research biomicroscope system has significantly improved 2D resolution (axial resolution of 28 ,m). Spectral Doppler imaging is also available, but in the absence of color Doppler, imaging times are increased and the detection of flow abnormalities is more difficult. M-mode imaging is available and equivalent to the clinical ultrasound system. Overall, the research system, given its higher 2D resolution, is best suited for in-depth analysis of mouse fetal cardiovascular structure and function, while the clinical ultrasound systems, equipped with phase array transducers and color Doppler imaging, are ideal for high-throughput fetal cardiovascular screens. [source] From kidney to cardiovascular diseases: NGAL as a biomarker beyond the confines of nephrologyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2010D. Bolignano Eur J Clin Invest 2010; 40 (3): 273,276 Abstract Neutrophil gelatinase-associated lipocalin (NGAL), a small 25 kDa stress-protein released from injured tubular cells after various damaging stimuli, is already known by nephrologists as one of the most promising biomarkers of incoming Acute Kidney Injury. Moreover, recent studies seem to suggest a potential involvement of this factor also in the genesis and progression of chronic kidney diseases. This brief review explores the new interesting involvement of NGAL in the experimental and clinical field of cardiovascular diseases, such as the pathogenesis and clinical manifestations of atherosclerosis, acute myocardial infarction and heart failure. It does not seem difficult that, in the next future, NGAL may become a new missing link between the kidney and the cardiovascular system. [source] Basal TSH levels compared with TRH-stimulated TSH levels to diagnose different degrees of TSH suppression: diagnostic and therapeutic impact of assay performanceEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2002M. Christ-Crain Abstract Background The estimated prevalence of endogenous subclinical hyperthyroidism varies from 4% to 6% and a basal thyroid stimulating hormone (TSH) level < 0·5 mU L,1 may be associated with increased mortality in subjects over 60 years of age who are not on thyroid medication. Exogenous TSH suppression is a mainstay in the treatment of thyroid cancer. Because of recent concerns about potential adverse effects, especially of endogenous TSH suppression on bone, the cardiovascular system and cognitive functions, subclinical hyperthyroidism obtained new clinical importance. We therefore re-evaluated the diagnostic value of basal and thyrotrop in TRH-stimulated serum TSH measurements using TSH assays with different sensitivities. Materials and methods A total of 805 oral and nasal TRH stimulation tests were performed on 409 ambulatory subjects with low basal serum TSH concentrations of less than 0·1 mIU L,1. Basal serum TSH was measured either using a second generation assay (functional sensitivity > 0·03 mIU L,1) or two third generation assays (functional sensitivity 0·01 mIU L,1 and 0·007 mU L,1, respectively). Serum TSH concentration was determined before and 3 h after oral administration of 40 mg of TRH and before and 30 min after nasal administration of 2 mg of TRH. Results In the oral testing group, the basal TSH levels measured by the different TSH assays were 0·06 ± 0·03, 0·04 ± 0·02 and 0·03 ± 0·02, respectively, whereas the peak TSH levels were 0·4 ± 0·6, 0·4 ± 0·6 and 0·3 ± 0·5 in the patients with subclinical hyperthyroidism. In overt hyperthyroidism, the basal TSH levels were 0·06 ± 0·02, 0·03 ± 0·02 and 0·03 ± 0·02, whereas the peak TSH levels were 0·19 ± 0·3, 0·16 ± 0·3 and 0·15 ± 0·2, respectively. Basal TSH values could discriminate between different degrees of TSH suppression if measured with a third generation assay (P < 0·001), but not with a second generation assay. There was only a weak correlation between basal TSH and peak TSH when measured by a second generation assay (n = 126; r = 0·3; P < 0·001) in contrast to the strong correlation found using the third generation assays (n = 128; r = 0·7; P < 0·001 and n = 69; r = 0·8; P < 0·001, respectively). Conclusions In view of the recent concerns about potential adverse effects in TSH suppression and based on our data, it is mandatory to select a TSH assay with a functional sensitivity of , 0·01 mIU L,1 for optimal titration of L-T4 suppressive therapy, especially in patients with thyroid cancer. If, however, only a second generation TSH assay is available, additional TRH testing allows a more careful titration of suppressive thyroxine therapy. [source] Effect of deep brain stimulation of the posterior hypothalamic area on the cardiovascular system in chronic cluster headache patientsEUROPEAN JOURNAL OF NEUROLOGY, Issue 9 2007P. Cortelli The objective of this study was to determine the cardiovascular effects of chronic stimulation of the posterior hypothalamic area (PHA) in cluster headache (CH) patients. Systolic and diastolic blood pressure (SBP, DBP), cardiac output, total peripheral resistance (TPR), heart rate (HR) and breathing were monitored at supine rest and during head-up tilt test (HUTT), Valsalva manoeuvre, deep breathing, cold face test and isometric handgrip in eight drug-resistant chronic CH patients who underwent monolateral electrode implantation in the PHA for therapeutic purposes. Autoregressive power spectral analysis (PSA) of HR variability (HRV) was calculated at rest and during HUTT. Each subject was studied before surgery (condition A) and after chronic deep brain stimulation (DBS) of PHA (condition B). Baseline SBP, DBP, HR and cardiovascular reflexes were normal and similar in both conditions. With respect to condition A, DBP, TPR and the LF/HF obtained from the PSA of HRV were significantly (P < 0.05) increased during HUTT in condition B. In conclusion, chronic DBS of the PHA in chronic CH patients is associated with an enhanced sympathoexcitatory drive on the cardiovascular system during HUTT. [source] Molecular genetics of pseudoxanthoma elasticumEXPERIMENTAL DERMATOLOGY, Issue 4 2001F. Ringpfeil Abstract: Pseudoxanthoma elasticum (PXE), a systemic heritable connective tissue disorder, is characterized by progressive calcification of elastic structures in the skin, the eyes and the cardiovascular system, with considerable intra- and interfamilial phenotypic variability. Recently, underlying genetic defects have been identified in the ABCC6 gene, which resides on the chromosomal locus 16p13.1 and encodes the MRP6 protein, a member of the ATP-binding cassette (ABC) family of proteins. The affected individuals are homozygous or compound heterozygous for a spectrum of genetic lesions, including nonsense and missense mutations, or deletions and splice-site alterations, confirming the autosomal recessive nature of this condition. Analysis of the deduced primary sequence suggests that MRP6 is a transmembrane transporter, but its function has not been delineated yet. Surprisingly, however, MRP6 is expressed primarily, if not exclusively, in the liver and the kidneys, suggesting that PXE may be a primary metabolic disorder with secondary involvement of elastic fibers. Identification of mutations in the ABCC6 gene in PXE provides a means for prenatal and presymptomatic testing in families at risk for recurrence. DNA-based analyses will also identify heterozygous carriers who may be at risk for development of limited manifestations of the disease as a result of compounding genetic factors and/or environmental modifiers. [source] The mammalian exercise pressor reflex in health and diseaseEXPERIMENTAL PHYSIOLOGY, Issue 1 2006Scott A. Smith The exercise pressor reflex (a peripheral neural reflex originating in skeletal muscle) contributes significantly to the regulation of the cardiovascular system during exercise. Exercise-induced signals that comprise the afferent arm of the reflex are generated by activation of mechanically (muscle mechanoreflex) and chemically sensitive (muscle metaboreflex) skeletal muscle receptors. Activation of these receptors and their associated afferent fibres reflexively adjusts sympathetic and parasympathetic nerve activity during exercise. In heart failure, the cardiovascular response to exercise is augmented. Owing to the peripheral skeletal myopathy that develops in heart failure (e.g. muscle atrophy, decreased peripheral blood flow, fibre-type transformation and reduced oxidative capacity), the exercise pressor reflex has been implicated as a possible mechanism by which the cardiovascular response to physical activity is exaggerated in this disease. Accumulating evidence supports this conclusion. This review therefore focuses on the role of the exercise pressor reflex in regulating the cardiovascular system during exercise in both health and disease. Updates on our current understanding of the exercise pressor reflex neural pathway as well as experimental models used to study this reflex are presented. In addition, special emphasis is placed on the changes in exercise pressor reflex activity that develop in heart failure, including the contributions of the muscle mechanoreflex and metaboreflex to this pressor reflex dysfunction. [source] Transgenic Animals in Cardiovascular Disease ResearchEXPERIMENTAL PHYSIOLOGY, Issue 6 2000Michael Bader Worldwide, the highest morbidity and mortality results from such cardiovascular diseases as hypertension, myocardial infarction, cardiac and renal failure, as well as stroke. Since the cardiovascular system and its regulation is quite complex, study of these disorders has been grossly limited to whole organism models. As a result, in recent years, transgenic technology has played a significant role in the discovery of specific gene products for cardiovascular regulation and disease aetiology. Genetic manipulation in rats and mice has altered the expression of numerous genes. In this review, some of the important new genetically modified animals (i.e. transgenic models) with alterations in hormone and second messenger systems involved in cardiovascular regulation are summarized. [source] | |||||||||||||||||||||||||||||||||||||||||||