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

The increase in natriuretic peptides (NP), atrial natriuretic factor (ANF), and brain natriuretic peptide (BNP) production and release by cardiocytes that occurs in hypertension has been considered to be a compensatory mechanism against ventricular overload. Studies on NP production in the spontaneously hypertensive rat (SHR), an experimental model of human hypertension, have produced controversial results and were carried out when hypertension was already established (> 17 weeks). At this time, age-related physiologic and molecular changes in cardiac muscle are difficult to separate from those related to hypertension, ie, increased ANF production and plasma levels. In addition, most of the studies used male rats because the rate of increase in arterial blood pressure--as well as the level to which it rises--is greater in males than in females. Studies of a similar nature using female SHR are not available. The aim of this work was to determine 1) whether ANF and BNP production and secretion increase with the development of hypertension in genetically hypertensive rats; 2) whether a sexual dimorphism in ANF and BNP production and secretion is present in the genetically hypertensive rat during the development of hypertension; and 3) whether the demand for ANF and BNP is the same from each chamber of the heart under these experimental conditions. Age-matched male and female SHR, Wistar-Kyoto (WKY), and Sprague Dawley (SD) rats at 2, 4, and 8 weeks of age were used. The normotensive SD were included to provide a wider basis for baseline findings, as WKY rats are not always a suitable control for SHR due to genetic variations. Natriuretic peptide plasma levels and tissue content were measured by radioimmunoassay. ANF, BNP, as well as alpha- and beta-myosin heavy chain (MHC) mRNA were estimated by Northern blot analysis. Blood pressure (BP) of more than 150 mm Hg was found only in 8-week-old male SHR. Plasma immunoreactive (ir)ANF and irBNP increased significantly at puberty (8 weeks) in both male and female SHR. The earliest molecular change encountered during the development of hypertension was a significant increase in BNP mRNA in the right and left atria from both male and female 8-week-old SHR. In the ventricles from both male and female SHR, there was no increase in the ratio of left ventricular wet weight/body weight, no increase in ventricular ANF mRNA transcripts, and no myosin heavy chain isoform switch (a protein marker of hypertrophy). irBNP ventricular concentration, however, increased significantly in both male and female SHR, but only in female SHR was there a concomitant increase in BNP mRNA. These results suggest that 1) ANF and BNP production are not coordinated in all cardiac compartments during the development of hypertension; 2) upregulation of BNP in the atria from male and female SHR is the earliest event detected at 8 weeks; 3) the prehypertensive stage, in the genetically hypertensive female rats, is associated with an increase in ventricular irBNP concentration and BNP mRNA; 4) there is a dissociation between BP and plasma levels of NP; and 5) as well, there is a dissociation between NP gene expression and MHC isoform switch. The regulation of NP is not coordinated in either gender during the development of hypertension. The activation of the BNP gene in female SHR suggests that BNP might play an important role at the onset of hypertension.
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PMID:Atrial natriuretic factor and brain natriuretic peptide gene expression in the spontaneous hypertensive rat during postnatal development. 971 95

Phenotypic modulation of smooth muscle cells is closely associated with vasculogenesis, enterogenesis and some diseases such as atherosclerosis, hypertension and leiomyogenic tumorigenicity. During phenotypic modulation, smooth muscle cells change their morphology, cell function and biochemical characteristics. Recent studies have focused on the regulation mechanism of smooth muscle cell-specific genes at the levels of transcription and/or alternative splicing in a phenotype-dependent manner. Typical examples of such genes include caldesmon, alpha-tropomyosin, myosin heavy chain, SM22, calponin and alpha 1 integrin. Cell adhesion molecules and growth factors/cytokines also play a critical role for controlling phenotype of smooth muscle cells via signal transduction pathways such as phosphoinositide 3-kinase and mitogen-activated protein kinases.
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PMID:Molecular mechanism of phenotypic modulation of smooth muscle cells. 972 87

Electrophoretic analyses of muscle proteins in whole muscle homogenates and single muscle fiber segments were used to examine myosin heavy chain (MHC) and myosin light chain 2 (MLC2) isoform composition and fiber type populations in soleus muscles from spontaneously hypertensive rats (SHRs) and their age-matched normotensive controls [Wistar-Kyoto (WKY) rats], at three stages in the development of high blood pressure (4 wk, 16 wk, and 24 wk of age). Demembranated (chemically skinned with 2% Triton X-100), single fiber preparations were used to determine the maximum Ca2+-activated force per cross-sectional area, calcium sensitivity, and degree of cooperativity of the contractile apparatus and Ca2+-regulatory system with respect to Ca2+. The results show that, at all ages examined, 1) SHR soleus contained a lower proportion of MHCI and MLC2 slow (MLC2s) and a higher proportion of MHCIIa, MHCIId/x, and MLC2 fast (MLC2f ) isoforms than the age-matched controls; 2) random dissection of single fibers from SHR and WKY soleus produced four populations of fibers: type I (expressing MHCI), type IIA (expressing MHCIIa), hybrid type I+IIA (coexpressing MHCI and MHCIIa), and hybrid type IIA+IID (coexpressing MHCIIa and MHCIId/x); and 3) single fiber dissection from SHR soleus yielded a lower proportion of type I fibers, a higher proportion of fast-twitch fibers (types IIA and IIA+IID), and a higher proportion of hybrid fibers (types I+IIA and IIA+IID) than the homologous muscles from the age-matched WKY rats. Because the presence of hybrid fibers is viewed as a marker of muscle transformation, these data suggest that SHR soleus undergoes transformation well into adulthood. Our data show also that, for a given fiber type, there are no significant differences between SHR and WKY soleus muscles with respect to any of the Ca2+-activation properties examined. This finding indicates that the lower specific tensions reported in the literature for SHR soleus muscles are not due to strain- or hypertension-related differences in the function of the contractile apparatus or regulatory system.
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PMID:Fiber type populations and Ca2+-activation properties of single fibers in soleus muscles from SHR and WKY rats. 1006 90

In an in vivo study, spontaneously hypertensive rats (SHR) were treated with an angiotensin II (Ang II) type 1 receptor antagonist of candesartan or hydralazine. Untreated SHR progressively developed severe hypertension, and treatment with candesartan or hydralazine decreased blood pressure. Candesartan reduced left ventricular (LV) weight, LV wall thickness, transverse myocyte diameter, the relative amount of V3 myosin heavy chain, and interstitial fibrosis, while treatment with hydralazine slightly prevented an increase in LV wall thickness, but did not exert a significant reduction on other parameters. In an in vitro study, neonatal rat cardiomyocytes were cultured on deformable silicone dishes. Stretching cardiomyocytes activated second messengers such as protein kinase C, Raf-1 kinase, and mitogen-activated protein (MAP) kinase, increasing protein synthesis, enhancing endothelin (ET)-1 release, activating the Na+/H+ ion exchanger. Moreover, pretreatment with candesartan diminished an increase in phenylalanine incorporation, MAP kinase activity, and c-fos gene expression induced by the stretching of cardiomyocytes. This suggests that the cardiac renin-angiotensin system is linked to the formation of pressure-overload hypertrophy and that Ang II increases the growth of cardiomyocytes by an autocrine mechanism. Finally, we examined the signalling pathways leading to MAP kinase activation both in cardiac myocytes and in cardiac fibroblasts. Ang II-evoked signal transduction pathways differed between cell types. In cardiac fibroblasts, Ang II activated MAP kinase through a pathway including the Gbetagamma subunit of Gi protein, Src, Shc, Grb2, and Ras, while Gq and protein kinase C were important in cardiac myocytes.
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PMID:Role of tissue angiotensin II in myocardial remodelling induced by mechanical stress. 1007 20

The aim of this study was to clarify the differences between the angiotensin II type 1 (AT1) receptor antagonist and the angiotensin-converting enzyme (ACE) inhibitor on smooth muscle and nonmuscle myosin heavy chain isoforms in aortic smooth muscle cells of Wistar-Kyoto rats and spontaneously hypertensive rats. All 4 myosin heavy chain isoforms are heterogeneously expressed in the smooth muscle cells of the aortic tunica media in 20-week-old rats, and the contractile-type myosin heavy chains are highly expressed in smooth muscle cells of the aortic tunica media compared with the synthetic-type myosin heavy chains. Both the AT1 receptor antagonist and the ACE inhibitor had the same effects on hemodynamics, smooth muscle cell hypertrophy and proliferation, fibrosis, and vascular remodeling in spontaneously hypertensive rats. However, the AT1 receptor antagonist had a more potent effect on the downregulation of the synthetic-type myosin heavy chains than the ACE inhibitor in spontaneously hypertensive rat aortic tunica media. In contrast, these effects of the AT1 receptor antagonist and the ACE inhibitor on hemodynamics, morphology, fibrosis, and expression of myosin heavy chain isoforms in smooth muscle cells of the aortic tunica media were not observed in Wistar-Kyoto rats. Thus, within 6 weeks, the AT1 receptor antagonist might modulate the cellular composition of myosin heavy chain isoforms in smooth muscle cells more efficiently than the ACE inhibitor, without morphological changes in the spontaneously hypertensive rat aorta.
Hypertension 1999 Apr
PMID:Angiotensin II type 1 receptor antagonist downregulates nonmuscle myosin heavy chains in spontaneously hypertensive rat aorta. 1020 33

In elderly patients, aortic stiffness is a major determinant of increased end-systolic stress leading to left ventricular (LV) hypertrophy with impaired cardiac performance. However, in a rat model of aortic elastocalcinosis (induced by vitamin D(3)-nicotine [VDN] treatment), brief exposure (1 month) to increased aortic stiffness modified neither cardiac function nor cardiac structure. Here we report the impact of longer exposure (3 months) to aortic stiffness. Three months after induction of aortic stiffness, aortic characteristic impedance was measured in awake rats, 8 control and 10 VDN. Stroke volume was measured (electromagnetic probe) at baseline and after acute volume overload. LV weight/body weight ratio, collagen, and myosin heavy chain (MHC) contents were determined. Although aortic characteristic impedance increased (controls, 32+/-2; VDN rats, 50+/-8 10(3) dyne. s/cm(5); P=0.0248), stroke volume was maintained in VDN rats at baseline (controls, 223+/-18; VDN, 211+/-13 microL) and after volume overload (controls, 378+/-14; VDN, 338+/-15 microL). However, LV weight/body weight ratio (controls, 1.54+/-0.07; VDN, 1.73+/-0.05 g/kg; P=0.0397) and LV collagen content (controls, 31+/-4; VDN, 52+/-4 microgram/g dry wt; P=0.0192) increased. A shift from alpha-MHC (controls, 82+/-2%; VDN, 69+/-3%; P=0.0056) to beta-MHC (controls, 18+/-2%; VDN, 31+/-3%; P=0. 0056) was also observed. Three months' exposure to increased aortic stiffness in VDN rats induced LV hypertrophy with moderate interstitial fibrosis and a shift in the MHC-isoform pattern. Such structural adaptation maintains LV performance.
Hypertension 1999 Jul
PMID:Cardiac consequences of prolonged exposure to an isolated increase in aortic stiffness. 1040 25

Mechanical stretch induced by high blood pressure is an initial factor leading to cardiac hypertrophy. In an in vivo study, an angiotensin II (AngII) type 1 receptor antagonist TCV116 reduced left ventricular (LV) weight, LV wall thickness, transverse myocyte diameter, relative amount of V3 myosin heavy chain, and interstitial fibrosis, while treatment with hydralazine did not. In an in vitro study using cultured cardiomyocytes, mechanical stretch activated second messengers such as mitogen-activated protein (MAP) kinase, followed by increased protein synthesis. Additionally, in the stretch-conditioned medium AngII and endothelin-1 concentrations were increased. Furthermore, the Na+/H+ exchanger activated by mechanical stretch modulated the hypertrophic responses of cardiomyocytes. The pathways leading to MAP kinase activation differed between cell types. In cardiac fibroblasts AngII activated MAP kinase via G beta gamma subunit of Gi, Src, Shc, Grb2, and Ras, whereas Gq and protein kinase C were critical in cardiomyocytes.
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PMID:The molecular mechanism of cardiac hypertrophy and failure. 1041 19

Hypertrophy is an adaptive response of the heart to hemodynamic overload such as hypertension. However, it is generally accepted that cardiac hypertrophy is one of the most critical risk factors of heart disease. Therefore, for the treatment of hypertension it is important to understand the mechanism of cardiac hypertrophy and to establish effective pharmaceutical interventions. Mechanical stretch induced by hypertension is an initial factor leading to cardiac hypertrophy. In an in vivo study using spontaneously hypertensive rats, an angiotensin II type 1 receptor antagonist, TCV116, decreased left ventricular weight, left ventricular wall thickness, transverse myocyte diameter, relative amount of V3 myosin heavy chain, and interstitial fibrosis, whereas treatment with hydrolazine did not. In an in vitro study using cultured cardiomyocytes of neonatal rats, mechanical stretch activated second messengers, such as extracellular signal-regulated protein kinase (ERK), followed by increased protein synthesis. Additionally, in the stretch-conditioned medium, the levels of angiotensin II and endothelin-1 concentrations were increased. Moreover, the Na+/H+ exchanger activated by mechanical stretch modulated the hypertrophic responses of cardiomyocytes. To further elucidate whether angiotensin II is indispensable for mechanical stress-induced cardiac hypertrophy, mechanical stretch-induced ERK activation was examined in angiotensin II type 1a receptor knock-out mice. Although the addition of angiotensin II had no effects on the ERK activity in cardiomyocytes of angiotensin II type 1a receptor knockout mice, mechanical stretch induced a larger increase in the ERK activity in cardiac myocytes from these mice compared with cardiac myocytes of wild-type mice. These results suggest that mechanical stretch could induce hypertrophic responses in cardiac myocytes even in the absence of angiotensin II. The pathways leading to ERK activation differed between cell types. In cardiac fibroblasts, angiotensin II activated ERK via the G(beta)gamma subunit of Gi, Src, Shc, Grb2, and Ras, whereas Gq and protein kinase C were critical in cardiomyocytes.
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PMID:Role of the renin-angiotensin system in cardiac hypertrophy. 1075 May 88

Inotropic responsiveness to beta-adrenergic stimulation is generally found to be impaired in left ventricular (LV) hypertrophy and failure. To investigate the mechanisms by which angiotensin-converting enzyme inhibitor therapy may modulate inotropic responsiveness with long-term pressure overload, we studied the effects of captopril treatment on cardiac gene expression, LV muscle mechanical contraction, and intracellular calcium (Ca(2+)) transients from spontaneously hypertensive rats (SHR). LV papillary muscles from untreated SHR, age-matched normotensive Wistar-Kyoto rats (WKY), and SHR treated with captopril (CAP(Rx) started at 12, 18, and 21 months of age) were studied. All animals were studied at 24 months of age or when heart failure developed. In untreated SHR, alpha-myosin heavy chain (MHC) gene expression and protein were decreased, the Ca(2+) transient (with the bioluminescent indicator aequorin) was prolonged, and abundance of Na(+)/Ca(2+) exchanger mRNA levels increased in comparison to WKY. Active stress development at L(max) and the maximum rate of stress development were depressed and contractile duration prolonged in SHR relative to WKY. Isoproterenol administration further decreased active stress in untreated SHR despite an increase in intracellular Ca(2+) levels. In CAP(Rx) SHR, alpha-MHC gene expression and protein levels were increased, the Ca(2+) transient was not prolonged, Na(+)/Ca(2+) exchanger expression was downregulated, and papillary muscle function demonstrated increased active stress and maximum rate of stress development in response to isoproterenol. The increased abundance of alpha-MHC mRNA in conjunction with an increase in V(1) myosin isozyme suggests that captopril affects transcriptional regulation of cardiac gene expression. Restored LV inotropic responsiveness to beta-adrenergic stimulation in CAP(Rx) SHR appears to be coupled to normalization of Na(+)/Ca(2+) exchanger mRNA expression, upregulation of V(1) myosin isozyme levels, and increased speed of contraction.
Hypertension 2000 Jun
PMID:Altered inotropic responsiveness and gene expression of hypertrophied myocardium with captopril. 1085 64

We investigated whether the imposition of chronic alcohol in hypertension leads to greater biochemical and cellular abnormalities of the myocardium than those arising in normotension. Fifteen-week-old spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were fed ethanol-containing diets for six weeks. Particular attention was focused on the composition of contractile proteins identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), fractional rate of protein synthesis, and synthesis rates relative to RNA (RNA activity) or DNA (cellular efficiency). In addition, myocardial enzymes and adenine nucleotides were measured. In both SHR and WKY rats chronic ethanol caused a general decrease in the contents of all nine contractile proteins with myosin heavy chain predominantly affected. Fractional rates of mixed (i.e., total) and myofibrillary proteins remained unaltered in both WKY rats and SHR, as were cellular efficiencies. The RNA activity was significantly reduced in ethanol-treated SHR but not in WKY rats. In ethanol-treated SHR, cardiac creatine kinase (CK) and malate dehydrogenase (MDH) activities were increased, AMP levels were elevated, whilst ATP levels and the energy charge were reduced. In WKY rats, the only significant change related to increased aspartate aminotransferase activities in response to alcohol feeding. Although there were only subtle differences between the response of the normotensive and hypertensive rats due to ethanol dosage, the reduced ATP levels and increased CK and MDH activities in SHR may reflect a greater susceptibility to ischaemic damage. Reduced contractile protein content, particularly myosin heavy chain, may contribute to contractile defects, a common feature of subclinical and clinical alcoholic cardiomyopathy.
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PMID:A comparative investigation into the effect of chronic alcohol feeding on the myocardium of normotensive and hypertensive rats: an electrophoretic and biochemical study. 1093 59


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