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

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

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

Cardiac phenotypic modulation and remodeling appear to be involved in the pathophysiology of cardiac hypertrophy and heart failure. We undertook this study to examine whether angiotensin II (Ang II) in vivo, independent of blood pressure, contributes to cardiac phenotypic modulation and remodeling. A low dose (200 ng/kg per minute) of Ang II was continuously infused into rats by osmotic minipump for 24 hours or 3 or 7 days to examine the effects on the expression of cardiac phenotype-related or fibrosis-related genes. This Ang II dose caused a small and gradual increase in blood pressure over 7 days. Left ventricular mRNAs for skeletal alpha-actin, beta-myosin heavy chain, atrial natriuretic polypeptide, and fibronectin were already increased by 6.9-, 1.8-, 4.8-, and 1.5-fold, respectively, after 24 hours of Ang II infusion and by 6.9-, 3.3-, 7.5-, and 2.5-fold, respectively, after 3 days, whereas ventricular alpha-myosin heavy chain and smooth muscle alpha-actin mRNAs were not significantly altered by Ang II infusion. Ventricular transforming growth factor-beta 1 and types I and III collagen mRNA levels did not increase at 24 hours and began to increase by 1.4-, 2.8-, and 2.1-fold, respectively, at 3 days. An increase in left ventricular weight occurred 3 days after Ang II infusion. Treatment with TCV-116 (3 mg/kg per day), a nonpeptide selective angiotensin type 1 receptor antagonist, completely inhibited the above-mentioned Ang II-induced increases in ventricular gene expressions and weight. Hydralazine (10 mg/kg per day), which completely normalized blood pressure, did not block cardiac hypertrophy or increased cardiac gene expressions by Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Jun
PMID:Angiotensin II induces cardiac phenotypic modulation and remodeling in vivo in rats. 776 70

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

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

We have identified and partially sequenced a soluble factor, myotrophin, from spontaneously hypertensive rat hearts and hypertrophic human hearts that enhances myocyte protein synthesis and stimulates myocardial cell growth. Our studies suggest that myotrophin may be a biochemical link between hemodynamic stress and myocardial cellular hypertrophy. When rat neonatal cardiac myocytes maintained in culture were incubated with myotrophin for 30 minutes, they showed a marked increase in c-myc, c-fos, and c-jun messenger RNA levels. Cardiac myocytes treated for 24 hours with myotrophin showed a fourfold increase in connexin 43 (gap junction protein), a sixfold increase in atrial natriuretic factor, a threefold increase in skeletal alpha-actin, and a threefold increase in total myosin transcript levels. Studies on myosin isoforms showed a selective increase in the beta-myosin heavy chain transcript levels but no reciprocal decrease in alpha-myosin heavy chain transcript levels. Our data suggested that myotrophin appears to be a primary modulator for myocardial cell growth and differentiation and may play an important role in the pathogenesis of cardiac hypertrophy. Myotrophin may be involved in the upregulation of myofibrillar protein and the activation of cardiac gene transcription during growth and hypertrophy of the myocardium, and the induction of early response gene expression may be linked to this response.
Hypertension 1993 Feb
PMID:Myotrophin induces early response genes and enhances cardiac gene expression. 842 77

Antihypertensive treatments were given to young and adult SHRs, to prevent and reverse hypertension, respectively. Cardiac hypertrophy and the steady state level of the "fetal" genes, ANP, alpha-skeletal actin (alpha-skA), and beta myosin heavy chain (beta-MHC) mRNAs were assessed. Our findings show that the reduction of blood pressure does not consistently result in a similar regression of the "fetal gene program".
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PMID:Molecular manifestations of cardiac hypertrophy in the spontaneously hypertensive rat effects of antihypertensive treatments. 854 Mar 96

We studied the effect of chronic (7 days) angiotensin II (Ang II) infusion in nonpressor and pressor doses on cardiovascular mass and expression of alpha- and beta-myosin heavy chain genes in the left ventricle in normotensive Wistar rats. An increased left ventricular mass was observed in rats receiving non-pressor and pressor doses of Ang II, but only high doses increased arterial pressure. Normalization of arterial pressure during Ang II infusion by losartan, a specific Ang II receptor antagonist, or hydralazine had different effects on left ventricular mass. Losartan prevented the increased left ventricular mass, and hydralazine did not affect left ventricular mass. Northern blot analysis showed that the switch in left ventricular myosin isoform mRNA from the adult to the fetal pattern occurred only in rats given the pressor Ang II dose. Both losartan and hydralazine, in parallel with the normalization of arterial pressure, prevented this myosin isoform switch. Thus, these data suggest that the Ang II-induced increase in left ventricular mass was not dependent on pressure overload, but the switch in myosin isoform mRNA from the adult to the fetal pattern was dependent on pressure overload.
Hypertension 1996 Aug
PMID:Angiotensin II increases left ventricular mass without affecting myosin isoform mRNAs. 870 92

The role of cyclic AMP-dependent protein kinase (PKA) and systolic function during the development of left ventricular hypertrophy (LVH) still remain uncertain. The aim of this work is to study PkA activity and mechanical heart function in two experimental heart hypertrophy models: specifically, one induced by pressure overload (Goldblatt model: two kidneys, one clamped, Gb); and another secondary to myocardial infarction (MI) generated by ligation of the left coronary artery. Hypertension in the Gb group becomes evident by the third and fourth week after surgery without any significant change in the corresponding sham group. The myocardial infarction group did not show any change in systolic pressure. Different degrees of LVH for the two experimental models were observed. Relative cardiac mass (RCM) and relative ventricular mass (RVM) increased 23 and 16%, respectively, above the sham-operated rats in MI group (P < 0.05). For the pressure overload model, the increase values were 42 and 44%, respectively (P < 0.05). Left ventricular hypertrophy was also evaluated through quantitative changes in cardiac beta-myosin heavy chain which agreed with morphometric studies in Goldblatt rats. Ventricular PKA activity did not show any significant difference with respect to the sham-operated group after induction of pressure overload. For the MI model, ventricular PKA activity changed only at day 7 post-infarction with a 289% increase above the sham-operated group (P < 0.05). The absence of activation of ventricular PKA after constriction of renal artery or myocardial infarction was also corroborated by the patterns of PKA-dependent phosphorylated proteins. While force-generating capacity was increased, there was no change in ventricular PKA activity, indicating that there is no relation between this enzyme and systolic stress-strain regression lines in either pressure overload or myocardial infarction conditions. Cyclic AMP-dependent protein kinase activity had no relation with development of cardiac hypertrophy in the two experimental models of LVH. These findings contribute to the hypothesis for a multifactorial interaction of different intracellular biochemical and molecular mechanisms in the genesis of cardiac hypertrophy.
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PMID:Cyclic AMP-dependent protein kinase and mechanical heart function in ventricular hypertrophy induced by pressure overload or secondary to myocardial infarction. 876 44

1. This study was undertaken to determine whether the AT1 receptor directly contributes to hypertension-induced cardiac hypertrophy and gene expressions. 2. Stroke-prone spontaneously hypertensive rats (SHRSP) were given orally an AT1, receptor antagonist (losartan, 30 mg kg-1 day-1), an angiotensin converting enzyme inhibitor (enalapril 10 mg kg-1 day-1), a dihydropyridine calcium channel antagonist (amlodipine, 5 mg kg-1 day-1), or vehicle (control), for 8 weeks (from 16 to 24 weeks of age). The effects of each drug were compared on ventricular weight and mRNA levels for myocardial phenotype- and fibrosis-related genes. 3. Left ventricular hypertrophy of SHRSP was accompanied by the increase in mRNA levels for two foetal phenotypes of contractile proteins (skeletal alpha-actin and beta-myosin heavy chain (beta-MHC)), atrial natriuretic polypeptide (ANP), transforming growth factor-beta-1 (TGF-beta 1) and collagen, and a decrease in mRNA levels for an adult phenotype of contractile protein (alpha-MHC). Thus, the left ventricle of SHRSP was characterized by myocardial transition from an adult to a foetal phenotype and interstitial fibrosis at the molecular level. 4. Although losartan, enalapril and amlodipine lowered blood pressure of SHRSP to a comparable degree throughout the treatment, losartan caused regression of left ventricular hypertrophy of SHRSP to a greater extent than amlodipine (P < 0.01). 5. Losartan significantly decreased mRNA levels for skeletal alpha-actin, ANP, TGF-beta 1 and collagen types I, III and IV and increased alpha-MHC mRNA in the left ventricle of SHRSP. Amlodipine did not alter left ventricular ANP, alpha-MHC and collagen types I and IV mRNA levels of SHRSP. 6. The effects of enalapril on left ventricular hypertrophy and gene expressions of SHRSP were similar to those of losartan, except for the lack of inhibition of collagen type I expression by enalapril. 7. Unlike the hypertrophied left ventricle, there was no significant difference between losartan and amlodipine in the effects on non-hypertrophied right ventricular gene expressions of SHRSP. 8. Our results show that hypertension causes not only left ventricular hypertrophy but also molecular transition of myocardium to a foetal phenotype and interstitial fibrosis-related molecular changes. These hypertension-induced left ventricular molecular changes may be at least in part mediated by the direct action of local angiotensin II via the AT1, receptor.
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PMID:Effects of an AT1 receptor antagonist, an ACE inhibitor and a calcium channel antagonist on cardiac gene expressions in hypertensive rats. 876 77


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