Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two antigenically distinct types of myosin heavy chain, referred to as alpha and beta, have been identified in autoptic and bioptic specimens of human heart using specific antimyosin antibodies. By immunofluorescence heavy chain alpha was present in all atrial myocytes and in a variable number of ventricular myocytes. Heavy chain beta was present in all ventricular myocytes and in a number of atrial myocytes. Ventricular hypertrophy in patients with aortic stenosis, systemic hypertension or tetralogy of Fallot was characterized by an almost complete absence of fibres reactive with anti-alpha. A striking decrease in alpha chain reactivity and a parallel increase in beta chain reactivity was apparent in the hypertrophied left atria of patients with mitral stenosis. To quantify these myosin changes a novel procedure was developed whereby myosin was extracted from single cryosections serial to those processed for immunofluorescence and the relative amount of alpha and beta heavy chain was determined by enzyme immunoassay. Heavy chain alpha was less than 5% in most normal ventricular specimens and disappeared completely under the effect of pressure overload. On the other hand heavy chain beta was generally undetectable in the left atrial myocardium but increased up to 90% in biopsies of hypertrophied atria.
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PMID:Myosin changes in hypertrophied human atrial and ventricular myocardium. A correlated immunofluorescence and quantitative immunochemical study on serial cryosections. 624 7

We have used affinity-purified antibodies reacting with guinea pig soleus muscle and ventricular myosin heavy chains to analyze the distribution of specific isomyosin in the ventricular myocardium of normal and renal hypertensive rats. Immunofluorescent staining of cardiac tissue sections with the two antimyosins revealed striking variations in reactivity among ventricular muscle fibers, reactive fibers being more numerous in the left compared to the right ventricle and in subendocardial compared to subepicardial layers. The response of the ventricular myocardium changed during development: all fibers were stained in the newborn rat, whereas most fibers were unreactive in 1-month-old animals. The number of reactive fibers increased again in subsequent stages leading to a mixed pattern in adult animals. The normal mixed pattern of reactivity was transformed into a uniformly positive pattern in hypertensive rats 2 months after surgery. This complete transformation was observed in 20 out of 23 hypertensive animals examined. These findings indicate that the two antimyosins cross-react with a particular type of ventricular myosin heavy chain, whose distribution varies in different muscle cells and whose relative concentration changes during development and during cardiac hypertrophy induced by systemic hypertension. We suggest that differences in pressure load may be responsible for both regional variations in isomyosin distribution and for isomyosin changes in hypertensive animals.
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PMID:Isomyosin distribution in normal and pressure-overloaded rat ventricular myocardium. An immunohistochemical study. 645 85

Previous studies have shown that both systemic hypertension induced by abdominal aortic constriction (Abcon) and 50% caloric restriction (CR) increase left ventricular (LV) beta-myosin heavy chain (MHC) protein expression in the rat. However, these two physiological states have different effects on hemodynamic load, and information regarding beta-MHC localization across the LV wall in these two models may provide insight into the process of adaptation to chronic stress among myocardial cells. Thus the goal of this study was to determine the pattern of beta-MHC protein expression across the LV wall in Abcon and CR models using a beta-MHC-specific antibody. Adult female Sprague-Dawley rats (approximately 225-250 g) were randomly assigned to one of three groups: 1) normal control (NC), 2) Abcon, and 3) CR. After a treatment period of 5 wk, Abcon LVs hypertrophied 52% relative to NC, accompanying the 42% increase in mean blood pressure. CR rats, however, had a normal LV weight-to-body weight ratio. The relative content of LV beta-MHC protein expression, as assessed by native gel electrophoresis, increased from 3% in NC to 25 and 41% in Abcon and CR rats, respectively. Immunohistochemical analysis of beta-MHC expression demonstrated that the increase in beta-MHC protein in the Abcon group occurred primarily on the endocardial side of the LV. In contrast, the increase in beta-MHC protein in the CR LV occurred equally across the entire LV wall. This suggests that CR has a global effect on MHC isoform expression in LV myocardial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunolocalization of rat cardiac beta-MHC protein expression in systemic hypertension and caloric restriction. 748 43

We examined the relationship between cardiac hypertrophy, myosin heavy chain (MHC) isoform expression, and production of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) before and after the development of DOCA-salt hypertension. DOCA-salt rats exhibited significant left ventricular hypertrophy at the prehypertensive stage (1 week of treatment), without MHC isoform switch or change in natriuretic peptide gene expression. In the hypertensive stage (5 weeks of treatment), pronounced left ventricular hypertrophy was observed, and this was characterized by an increase in beta-MHC protein, resulting in a switch from 90% alpha-MHC to 51% alpha-MHC and 49% beta-MHC. ANF and BNP mRNA levels and peptide content were significantly increased at this stage. Unexpectedly, the MHC isoform switch was evident in the non-hypertrophied right ventricle to the same degree as in the left ventricle. Natriuretic peptide production was also increased in the right ventricle at 5 weeks of treatment, but to a lesser degree than in the left ventricle. In contrast, in the hypertrophied left atrium there was no MHC isoform switch, while ANF and BNP mRNA levels were augmented. Plasma ANF was significantly increased in the prehypertensive stage; this was accompanied by a partial depletion of atrial ANF stores. Plasma BNP was increased only in the hypertensive stage, reflecting an increase in ventricular BNP synthesis and secretion. These results suggest that 1) cardiac hypertrophy, MHC isoform expression, and stimulation of natriuretic peptide production are processes that may be dissociated from each other; 2) increases in plasma ANF without a concomitant increase in plasma BNP reflect atrial hemodynamic overload, while increases in both ANF and BNP in plasma are associated with ventricular hypertrophy; and 3) there exist differences in the storage, secretion, and processing patterns of ANF and BNP in the atria.
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PMID:Dissociation of cardiac hypertrophy, myosin heavy chain isoform expression, and natriuretic peptide production in DOCA-salt rats. 754 Aug 47

A study was undertaken to determine how variations in chronic pressure overload imposed on the left ventricle (LV) regulate both its mass and the relative level of expression of the slow beta-myosin heavy chain (MHC) in rodents. Systemic mean arterial pressure was varied by the following interventions: 1) abdominal aortic constriction (AbCon), 2) unilateral nephrectomy coupled with salt and deoxycorticoacetate treatment (Nx-D), and 3) treatment with the angiotensin II-converting enzyme inhibitor captopril (50 mg.kg-1.day-1) in combination with the other interventions. Results showed that both AbCon and Nx-D induced significant elevations in both beta-MHC protein and mRNA expression relative to the control state. beta-MHC expression (protein and mRNA) strongly correlated with blood pressure as well as LV mass over a wide range. Although captopril treatment significantly reversed the elevations in mean arterial pressure, LV mass, and beta-MHC content in the AbCon group, it had very little effect on these variables in the Nx-D group. Collectively, the results demonstrate that the expression of beta-MHC in the rodent heart is strongly dependent on the arterial pressure imposed on LV. Although the underlying mechanisms have not been elucidated fully as to how alterations in blood pressure are translated to the regulation of the beta-MHC gene expression, these findings suggest that the renin-angiotensin system is not an obligatory factor for inducing cardiac hypertrophy or beta-MHC expression in some models of hypertension.
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PMID:Pressure-induced regulation of myosin expression in rodent heart. 761 60

Vascular smooth muscle cells (VSMC) are the principal cellular component of the blood vessel wall. Atherosclerosis, hypertension, and angiogenesis are associated with abnormal VSMC growth. Angiotensin II is hypertrophic for cultured adult rat aortic VSMC, whereas platelet-derived growth factor and serum are hyperplastic. To identify changes in specific proteins associated with either hyperplastic or hypertrophic growth, high resolution two-dimensional gel electrophoresis was performed on extracts from quiescent rat aortic VSMC and from VSMC exposed for 24 h to growth factors (10% fetal calf serum, platelet-derived growth factor, or angiotensin II). 12 proteins were up-regulated and 5 down-regulated by treatment with growth factors. Eight of the up-regulated and one of the down-regulated proteins were identified by internal protein microsequencing from electroblotted two-dimensional gels or by co-electrophoresis of purified proteins in two-dimensional gels. Four of the proteins up-regulated by growth factors were identified as mediators of protein folding. These were heat shock proteins, HSP-60 and HSP-70, protein disulfide isomerase, and protein disulfide isomerase isozyme Q-2. Additional proteins were identified as elongation factor EF-1 beta, a component of the protein synthesis apparatus, and calreticulin, another putative molecular chaperone. Vimentin and actin were also up-regulated, whereas an isoform of myosin heavy chain was down-regulated. Hyperplastic and hypertrophic growth were accompanied by similar changes in protein expression, suggesting that both types of growth require up-regulation of the protein synthesis and folding machinery.
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PMID:Components of the protein synthesis and folding machinery are induced in vascular smooth muscle cells by hypertrophic and hyperplastic agents. Identification by comparative protein phenotyping and microsequencing. 767 76

Previous studies show that elevations in blood pressure induce concomitant increases in both cardiac mass and slow beta-myosin heavy chain (MHC) expression in rodents, whereas caloric restriction of 50% (CR) causes an increase in beta-MHC while modestly lowering blood pressure in normotensive rats. The goals of this study were to 1) determine if beta-MHC expression could be independently regulated by CR and hypertension when these two interventions are combined and 2) determine if CR exerts a lowering of blood pressure in two contrasting models of rodent hypertension. Rodents were assigned to the following groups: 1) normal control (NC); 2) abdominal aortic constriction (Abcon), a model that induces hypertension via renin-angiotensin II; 3) nephrectomy-deoxycorticosterone acetate treatment (DOCA), a model that induces hypertension through increased salt retention; 4) CR; 5) Abcon+CR; 6) DOCA+CR. Results show that both Abcon and DOCA induced significant increases in systemic blood pressures, left ventricular (LV) weight/body weight, and the relative content of beta-MHC compared with NC. When applied in combination with either Abcon or DOCA, CR significantly blunted the changes observed in both systemic blood pressures and LV weight/body weight. In contrast, CR in conjunction with DOCA augmented % beta-MHC expression relative to either DOCA or CR alone. These data suggest 1) caloric restriction exerts a powerful impact on reducing experimentally induced hypertension in rodents and 2) the regulation of beta-MHC expression appears to be regulated by at least two processes, one associated with the stimulus of hypertension and the other involving an independent pathway linked to caloric restriction.
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PMID:Interaction of hypertension and caloric restriction on cardiac mass and isomyosin expression. 784 Mar 36

Adaptive cardiac hypertrophy in the rat has been characterized as pathological or physiological reflecting the nature of the inciting stimulus. These two adaptations are distinguished by alterations in contractility and in the myosin ATPase composition of the affected muscle. We investigated the relative amounts of the mRNAs encoding cardiac sarcoplasmic reticular calcium ATPase (SERCA2), cardiac and skeletal troponin I (TnI), atrial natriuretic factor (ANF), and myosin light chain 1 (MLC1) in the hearts of rats that had been subjected to either conditioning by swimming (Sw), to renovascular hypertension (H) or to the combined stimulus (H-Sw) for 6 weeks. Compared to control animals, the mRNA levels for SERCA2 and cardiac TnI were slightly increased with Sw and moderately depressed with H. H-Sw animals showed a trend towards normalized mRNA levels for both genes. ANF mRNA levels were slightly elevated with Sw and markedly elevated with both H and H-Sw. MLC1 mRNA levels did not change with either or both stimuli. These data confirm that these two types of adaptive hypertrophy can be distinguished at the level of gene expression and suggest that the mechanical alterations seen in adaptive hypertrophy reflect a spectrum of pre-translational alterations which are not limited to changes in myosin heavy chain gene expression.
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PMID:Alterations in gene expression in the rat heart after chronic pathological and physiological loads. 819 70

Both genetically determined and artificially-induced hypertension lead to cardiac hypertrophy and shift the myosin heavy chain (MHC) expression to the beta-MHC form. The cause of this change in gene expression is unknown. To contribute to the understanding of this phenomenon, we correlated the MHC expression in the left ventricle with basal, Forskolin- and isoprenaline-stimulated adenylate cyclase activity (cAMP production of membrane fractions). We used two control rat strains [Wistar-Hagemann (WH), Wistar-Kyoto (WKY)] and several rat models of hypertension: one clip-one kidney (1C-1K), desoxycorticosterone-treated rats (DOCA), rats with reduced renal mass (RRM) and spontaneously hypertensive rats (SHR). The level of hypertension correlated positively with the degree of cardiac hypertrophy (P < 0.01) and negatively (P < 0.05) with cAMP production, e.g. the higher the degree of hypertension, the lower both basal and stimulated cAMP levels. In addition we found that the lower the basal, isoprenaline- and Forskolin-stimulated cAMP production the lower was the expression of the alpha-MHC isoenzyme (P < 0.05). Thus, our data suggest that the decreased alpha-MHC expression upon hypertension-induced cardiac hypertrophy could be mediated via decreased adenylate cyclase activity and thus decreased intracellular cAMP production.
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PMID:Correlation of myosin heavy chain expression in the rat with cAMP in different models of hypertension-induced cardiac hypertrophy. 839 91

The renin-angiotensin system has been implicated as a possible mediator of the cardiac adaptations that develop in response to chronic pressure overload. In order to explore this, we studied rats that had elevated plasma renin activity (PRA) secondary to 6 weeks of either dietary salt restriction or renovascular hypertension (Htn)--conditions that exert distinctly different loads on the myocardium. Separate groups of sham and Htn animals were maintained on a high salt diet that resulted in a relative (Htn) or absolute (sham) reduction in PRA. Heart weight and heart/body weight ratios were increased only in animals with Htn. The ratio of alpha/beta myosin heavy chain (MHC) mRNA was significantly decreased with Htn. This ratio was markedly increased with low salt and was not influenced by high salt intake. Thus, the circulating renin-angiotensin system does not appear to play a primary role in defining cardiac myosin heavy chain adaptations to hemodynamic loads. However, sodium restriction, either via its hemodynamic or humoral effects, is sufficient to induce a physiologic change in myosin heavy chain gene expression in rats.
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PMID:The influence of dietary salt and plasma renin activity on myosin heavy chain gene expression in rat hearts. 839 98


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