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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Causes of hypertension have been well scrutinized, whereas the secondary, disabling effects of high blood pressure are less well investigated. We have used a rat model of hypertension and developed a technique to study the secondary vascular smooth muscle component of the disorder. Banding patterns of myosin heavy chain isoforms from rat aortae were examined using denaturing electrophoresis, Western blotting, immunochemical identification, and degradation studies. Myofibrillar ATPase activities were also measured. Left ventricular hypertrophy and hypertension were induced in rats by aortic banding just proximal to the renal artery. Aortic banding increased the heart weight/body weight (mg/g) ratio from 2.8 to 3.8 and mean aortic weight by 53%. Two distinct myosin heavy chain isoforms, molecular masses of 204 and 200 kDa, were identified by 4% sodium dodecyl sulphate-polyacrylamide electrophoresis of crude aortic extracts from normal rats in a relative molar ratio of 1.54:1. The development of significant thickening of the aorta was marked by substantial increases in aortic wall smooth muscle content but was not associated with any changes in distribution of the isoforms. The band patterns obtained on gel electrophoresis were not the result of contamination by other proteins, as Western blotting studies with specific antibodies demonstrated that the isoforms were smooth muscle in origin and were not derived from nonmuscle myosin sources. Myofibrillar ATPase activity of aortic smooth muscle from hypertensive rats was increased. It is suggested that this increase may be the result of post-transcriptional alterations of one or more sarcomeric proteins involved in the regulation of smooth muscle contraction.
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PMID:Myosin heavy chain isoform distribution in normal and hypertrophied rat aortic smooth muscle. 182 1

Similar pathologic changes in atherosclerosis and hypertension suggest that some common mechanisms may underlie these two major vascular diseases. Both diseases are characterized by smooth muscle proliferation. The atherosclerotic lesion is characterized by proliferation of smooth muscle cells in the arterial intima of large arteries, leading to vascular occlusion, lipid accumulation, and thrombosis. Smooth muscle proliferation in hypertensive vascular disease again results in increased wall mass and a narrowed lumen. The small vessel change is though to be etiologic of the increased peripheral resistance of high blood pressure. At least in large vessels, the form of proliferation is quite different. Atherosclerosis shows a true cell proliferation. In contrast, smooth muscle cells from animals with hypertensive vascular disease show DNA replication without mitosis. The resulting endoreplication is suggestive of the forms of replication seen in differentiated sarcomeric muscle, particularly in cardiac myocytes.
Hypertension
PMID:Smooth muscle proliferation in hypertension. State-of-the-art lecture. 672 71

In this work we have studied the cardiologic clinical manifestations appearing in response to toxic aggression by Tityus discrepans venom, such as hypertension, hypotension, tachycardia and pulmonary acute oedema. These depend on changes in the organisation of cellular and subcellular components of cardiac tissues and probably correspond with the damage found in envenomed humans. To evaluate cardiac tissue subcellular response to Tityus discrepans venom, male C57/B1 adult mice were randomised into two groups: envenomed mice were intraperitoneally injected at a dose of 5 mg/Kg of body weight and controls received saline solution. Samples from cardiac tissue were prepared for electron microscopy study and observed in a Hitachi-300. The most relevant cardiac ultrastructural findings in this model showed diffuse disarray of the myofibrils and abnormal pattern of the bands in the sarcomera, contractile element disorganisation, degeneration of fibres and loss of the characteristic sarcomeric structure given the appearance of a lax tissue. One of the most prominent features was the presence of a remarkable perinuclear oedema and the perinuclear cistern exhibited indentations over its whole arrangement. The vascular endothelium of the microvessels exhibited alterations with evident cytoplasmic projections toward the lumen of the vessel. Mitochondria presented a condensed conformation. All findings were degenerative signs of the contractile apparatus. We suggest that any cardiac tissue damage produced by toxins present in this venom are responsible for some of the clinical manifestations in envenomed animals and patients.
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PMID:Cardiac ultrastructural alterations in mice inoculated with Tityus discrepans (Buthidae) venom. 1129 80

Ventricular hypertrophy due to genetic mutations of sarcomeric proteins or that associated with long-standing hypertension typically yields a cavity with hyperdynamic ejection, elevated diastolic pressures, and limited filling volumes. The net result is reduced reserve capacity, dyspnea with exertional intolerance, and chest discomfort despite normal appearing coronary vessels. In addition to pharmacologic therapy by agents having negative inotropic effects, recent studies have examined the potential of ventricular pacing using right apical pre-excitation as a treatment for these disorders. This form of pacing can increase end-systolic volume and reduce cavity obliteration in both forms of the disease, yet has no demonstrable acute benefit on diastolic function. Chronic therapy trials have yielded mixed results, with more favorable responses observed in older patients particularly those with hypertensive hypertrophic disease. These data have also highlighted the importance of enhancing systolic reserve rather than diastolic function as a key therapeutic effect from pacing therapy. This review discusses the mechanisms by which pacing with ventricular pre-excitation acutely influences ventricular function, and summarizes results of recent clinical trials, putting the data into perspective regarding the relative role of systolic versus diastolic effects in these patients.
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PMID:Mechanisms and efficacy of LV pre-excitation for patients with heart failure and supra-normal systolic function. 1149 49

Gprotein-coupled receptor kinases (GRKs) are known to be involved in the development of cardiac hypertrophy. Their exact role and subcellular distribution during cardiac hypertrophy and failure remain to be elucidated. We examined expression and subcellular distribution of GRK2 and GRK5 in the left ventricle of female spontaneously hypertensive heart failure (SHHF) rats at 6 months of age using Western blots and fluorescent confocal microscopy. GRK2 was expressed mainly in the Triton X-100 soluble fraction in the left ventricle with similar expression levels between SHHF and age-matched Wistar-Kyoto (WKY) rats. GRK2 had a striated pattern which colocalized with sarcomeric alpha-actinin and G protein in both SHHF and WKY rat myocytes and specifically accumulated in the intercalated disks of myocytes from SHHF but not WKY rats. GRK5 was expressed in both the Triton X-100 soluble fraction and Triton X-100 insoluble fraction in the left ventricle with similar expression levels between SHHF and WKY rats. GRK5 distributed diffusely in the cytoplasm in both SHHF and WKY rat myocytes and specifically accumulated in the nucleus of myocytes from SHHF but not WKY rats. GRK5 colocalized with coilin, the major component of the nuclear substructure involved in RNA synthesis and processing. The results suggest different roles for GRK2 and GRK5 in G-protein signaling and RNA biogenesis. Subcellular redistribution of GRK2 and GRK5 may be involved in cardiac hypertrophy resulting from chronic hypertension.
Hypertension 2002 Jun
PMID:Myocyte redistribution of GRK2 and GRK5 in hypertensive, heart-failure-prone rats. 1205 42

Caveolae are omega-shaped organelles of the cell surface. The protein caveolin-3, a structural component of cardiac caveolae, is associated with cellular signaling. To investigate the effect of adenovirus-mediated overexpression of caveolin-3 on hypertrophic responses in cardiomyocytes, we constructed an adenovirus that encoded human wild-type caveolin-3 (Ad.Cav-3), mutant caveolin-3 (Ad.Cav-3Delta), or bacterial beta-galactosidase (Ad.LacZ). This mutant has been reported to cause human limb-girdle muscular dystrophy. It lacks 9 nucleotides in the caveolin scaffolding domain and behaves in a dominant-negative fashion. Rat neonatal cardiomyocytes were infected with the virus and then harvested 36 hours after infection. In noninfected cells, phenylephrine (PE) and endothelin-1 (ET) increased cell size and [3H]leucine incorporation, along with the induction of sarcomeric reorganization and the reexpression of beta-myosin heavy chain, indicating myocyte hypertrophy. Infection with Ad.LacZ had no effect on those parameters. Ad.Cav-3 prevented the PE- and ET-induced increases in cell size, leucine incorporation, sarcomeric reorganization, and reexpression of beta-myosin heavy chain. Ad.Cav-3 also blocked the PE- and ET-induced phosphorylations of extracellular signal-regulated kinases (ERKs) but did not affect c-Jun amino-terminal kinase and p38 mitogen-activated protein kinase activities. In contrast, Ad.Cav-3Delta significantly augmented hypertrophic responses to ET, which were associated with increased ET-induced phosphorylation of ERK1/2. These results suggest that caveolin-3 behaves as a negative regulator of hypertrophic responses, probably through suppression of ERK1/2 activity.
Hypertension 2003 Aug
PMID:Adenovirus-mediated overexpression of caveolin-3 inhibits rat cardiomyocyte hypertrophy. 1284 14

Molecular signaling that induces cardiac hypertrophy and dilated cardiomyopathy and the transition to decompensation is complex and poorly understood. Extrinsic hemodynamic stresses such as hypertension as well as intrinsic stresses such as genetic defects in sarcomeric proteins and cytoskeletal proteins trigger the process. Both stresses lead to similar outcomes of altered contractility and eventually heart failure. Activation of G-protein coupled receptors initiates cascades of signaling pathways, which promote cardiac hypertrophy by phosphorylation of transcriptional factors and changes in gene expression. Stimulation of these signaling molecules also activates a variety of kinases and phosphatases that induce altered phosphorylation of myofilament proteins. In this review, we focused on these functional effects of small G-protein, Ras and Rho, signaling pathways that reside within the cytoplasm downstream of membrane receptors and upstream of the transcriptional factors. It has been demonstrated that phosphorylation of myofilament proteins alter mechano-energetics of myofilament and contractile function of the heart. Therefore, understanding the role of low molecular weight G-proteins in both cardiac and vascular biology has become particularly important in view of the development of specific inhibitors of effectors of small G-proteins such as p38 MAP kinase and Rho-dependent kinase.
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PMID:Cardiac sarcomeric function, small G-protein signaling, and heart failure. 1646 22

Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by ventricular dilatation and impaired systolic function. Patients with DCM suffer from heart failure, arrhythmia, and are at risk of premature death. DCM has a prevalence of one case out of 2500 individuals with an incidence of 7/100,000/year (but may be under diagnosed). In many cases the disease is inherited and is termed familial DCM (FDC). FDC may account for 20-48% of DCM. FDC is principally caused by genetic mutations in FDC genes that encode for cytoskeletal and sarcomeric proteins in the cardiac myocyte. Family history analysis is an important tool for identifying families affected by FDC. Standard criteria for evaluating FDC families have been published and the use of such criteria is increasing. Clinical genetic testing has been developed for some FDC genes and will be increasingly utilized for evaluating FDC families. Through the use of family screening by pedigree analysis and/or genetic testing, it is possible to identify patients at earlier, or even presymptomatic stages of their disease. This presents an opportunity to invoke lifestyle changes and to provide pharmacological therapy earlier in the course of disease. Genetic counseling is used to identify additional asymptomatic family members who are at risk of developing symptoms, allowing for regular screening of these individuals. The management of FDC focuses on limiting the progression of heart failure and controlling arrhythmia, and is based on currently accepted treatment guidelines for DCM. It includes general measures (salt and fluid restriction, treatment of hypertension, limitation of alcohol intake, control of body weight, moderate exercise) and pharmacotherapy. Cardiac resynchronization, implantable cardioverter defibrillators and left ventricular assist devices have progressively expanding usage. Patients with severe heart failure, severe reduction of the functional capacity and depressed left ventricular ejection fraction have a low survival rate and may require heart transplant.
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PMID:Cardiomyopathy, familial dilated. 1683 24

The heart is a highly plastic organ capable of remodeling in response to changes in physiological or pathological demand. For example, when workload increases, compensatory hypertrophic growth of individual cardiomyocytes occurs to increase cardiac output. Sustained stress, however, such as that occurring with hypertension or following myocardial infarction, triggers changes in energy metabolism and sarcomeric protein composition, loss of cardiomyocytes, ventricular dilation, reduced pump function, and ultimately heart failure. It has been known for some time that autophagy is active in cardiomyocytes, occurring at increased levels in disease. Now, with recent advances in our understanding of molecular mechanisms governing autophagy, the potential contributions of cardiomyocyte autophagy to ventricular remodeling and disease pathogenesis are being explored. As part of this work, several recent studies have focused on autophagy in heart disease elicited by changes in hemodynamic load. Pressure overload stress elicits a robust autophagic response in cardiomyocytes that is maladaptive, contributing to disease progression. In this context, load-induced aggregation of intracellular proteins is a proximal event triggering autophagic clearance mechanisms. These findings in the setting of pressure overload contrast with protein aggregation occurring in a model of protein chaperone malfunction, where activation of autophagy is beneficial, antagonizing disease progression. Here, we review recent studies of cardiomyocyte autophagy in load-induced disease and address molecular mechanisms and unanswered questions.
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PMID:Autophagy in load-induced heart disease. 1905 38

The first classifications of cardiomyopathies from 1980 and 1996 described them as heart muscle diseases, with dilated (DCM), hypertrophic (HCM), restrictive (RCM), arrhythmogenic right ventricular (ARVC), and nonclassifiable cardiomyopathies. Furthermore, the World Health Organization/International Society and Federation of Cardiology (WHO/ISFC) classification from 1996 listed among the specific cardiomyopathies inflammatory cardiomyopathy as a new and distinct entity, which was defined histologically as myocarditis in association with cardiac dysfunction. Infectious and autoimmune forms of inflammatory cardiomyopathy were recognized. Viral cardiomyopathy was defined as viral persistence in a dilated heart without ongoing inflammation. If it was accompanied by myocardial inflammation, it was termed inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). This entity was further elucidated in a World Heart Federation consensus meeting in 1999 by quantitative immunohistological criteria (< 14 infiltrating cells/mm(2)) and the etiology by molecular biological methods, e.g., polymerase chain reaction, as viral, bacterial, or autoimmune (= nonmicrobial). The development of molecular genetics, with the discovery of a genetic background in several forms of cardiomyopathies previously alluded to as "of unknown origin", was the origin of a debate on a new classification based on genomics. A genomic/postgenomic classification was postulated taking the underlying gene mutations and the cellular level of expression of encoded proteins into account, thus distinguishing cytoskeleton (cytoskeletalopathies, e.g., DCM or ARVC), sarcomeric (sarcomyopathies as in HCM and RCM) and ion channel (channelopathies, e.g., long or short QT syndrome and Brugada's syndrome) cardiomyopathies. Such a classification of cardiomyopathies was proposed in 2006 by the American Heart Association (AHA), which took the rapid evolution of molecular genetics in cardiology into account. It also introduced several recently described diseases, and is unique in that it incorporated ion channelopathies even without hemodynamic dysfunction as a "primary" cardiomyopathy. The ESC (European Society of Cardiology) Working Group on Myocardial and Pericardial Diseases has deliberately taken a different approach based on a clinically oriented classification in which heart muscle disorders were grouped according to morphology and function. This obviously remains the clinically most useful approach for the diagnosis and management of patients and families with heart muscle disease. In the ESC position statement published in 2008, cardiomyopathies were defined as myocardial disorders in which the heart muscle is structurally and functionally abnormal, and in which coronary artery disease, hypertension, valvular and congenital heart disease are absent or do not sufficiently explain the observed myocardial abnormality. The aim was to help clinicians look beyond generic diagnostic labels in order to reach more specific diagnoses. In parallel, a scientific statement on the role of endomyocardial biopsy in the management of cardiovascular disease was published at the end of 2007 making useful recommendations for clinical practice and providing an understanding for the use of endomyocardial biopsy in an individual patient. Taking the classification of cardiomyopathies and the statement on the role of endomyocardial biopsies in different clinical scenarios together, the clinician is now able to identify genetic, autoimmune and viral causative factors by using a thorough and logical approach to reach a diagnosis in patients with familial and nonfamilial forms of the underlying structural heart muscle diseases.
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PMID:[Classification of cardiomyopathies and indication for endomyocardial biopsy revisited]. 1921 9


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