Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

The dihydropyridine calcium channel blocking agent amlodipine is an effective anti-hypertensive agent and its use (in doses of 5 or 10 mg/day/kg body weight) was investigated in male Wistar rats with hypertension induced by aortic constriction. Controls were sham-operated and pair-fed. At the end of the study, rates of protein synthesis were measured with radiolabelled phenylalanine to calculate fractional rates of protein synthesis (ks), absolute rates of protein synthesis (Vs) and synthesis rates relative to RNA (kRNA). After 30 days of aortic constriction, weights of the left ventricle and left atrium were significantly increased by hypertension. The weights of the right ventricle and right atrium were relatively unaffected. Hypertension was accompanied by significant increases in the protein and RNA contents of the left ventricle and left atrium. The contractile and non-contractile protein contents were also increased in the left ventricles of hypertensive rats as were total proteins and total RNA. In the myofibrillary fraction, ks decreased. The right ventricle and right atrium were generally unaffected except for a decline in mixed protein ks. Many of these changes in hypertension were ameliorated by treatment with amlodipine, particularly at the higher dose (i.e. 10 mg/kg body weight/day) implicating an effect on protein metabolism. In the left ventricle these included amelioration of the increases in mixed and contractile proteins, total RNA contents, mixed Vs and Vs for sarcoplasmic and stromal proteins. The ameliorating effects of amlodipine were moderate in the left atrium. Furthermore, amlodipine also retarded the hypertension-induced reduction in right ventricule rates of protein synthesis. Although the preceding study emphasises the preventative aspects of amlodipine's efficacy, an additional study was carried out in SHR rats to ascertain the applicability for regression per se. Amlodipine (10 mg/kg/body weight) therapy for 30 weeks caused regression of LV mass, total protein, RNA and DNA contents. We conclude that amlodipine, is an efficient agent in ameliorating the hypertension-induced changes in protein metabolism in an aortic constriction model.
...
PMID:Effects of the dihydropyridine calcium channel blocker amlodipine on ventricular and atrial protein synthesis in an aortic constriction model of hypertension and, following chronic treatment, in the left ventricle of SHR rats. 907 50

The principal stimulus that evokes pulmonary hypertension is chronic alveolar hypoxia. Pulmonary hypertension is associated with remodeling of the vessel walls, involving hypertrophy and hyperplasia of pulmonary arterial smooth muscle (PASM) and a concomitant increase in the deposition of connective tissue, resulting in increased wall thickness. The purpose of the present study was to determine the effect of hypoxia-induced hypertension on the structure and function of PASM. Experiments were designed to determine whether hypoxia-induced pulmonary hypertension is associated with alterations in PASM: 1) reactivity to a variety of agonists, 2) contractile protein proportions and isoforms, and 3) structural properties. Young adult male rats were made hypoxic by lowering the fraction of inspired O2 (10%) for 14 days. Pulmonary arterial segments were isolated and dose-response curves to various agonists (high K+, norepinephrine, serotonin, angiotensin II, and adenosine) were generated. Gel electrophoresis was used to measure changes in the relative amounts of actin or myosin and of myosin heavy chain (MHC) isoforms. Structural changes were correlated with the pharmacological and biochemical data. Hypoxia-induced pulmonary hypertension caused a general decreased reactivity, an increase in the proportion of nonmuscle to muscle MHC isoforms in PASM, and an increase in arterial wall thickness with PASM hypertrophy or hyperplasia.
...
PMID:Myosin isoform shifts and decreased reactivity in hypoxia-induced hypertensive pulmonary arterial muscle. 961 93

The transcriptional regulatory mechanisms that control gene expression during differentiation and contractile protein accumulation are becoming well understood in skeletal and cardiac muscle lineages. Current understanding of smooth muscle-specific gene transcription is much more limited, though recent studies have begun to shed light on this topic. In this review, we summarize some of the themes emerging from these studies and identify transcriptional regulatory elements common to several smooth muscle genes. These include potential binding sites for serum response factor, Sp1, AP2, Mhox, and YY1, as well as a potential transforming growth factor-beta control element. We speculate that it may be possible to manipulate smooth muscle-specific gene expression in asthma or pulmonary arterial hypertension as an eventual therapy.
...
PMID:Transcriptional regulation of smooth muscle contractile apparatus expression. 981 32

Various studies have shown the involvement of extracardiac tissues in hypertension, including the hepato-intestinal tract, musculo-skeletal system, skin, and the kidney. It was our hypothesis that these perturbations in non-cardiac tissues would also include alterations in protein metabolism. Thus, the reported differences in soleus contractile protein composition may be related to changes in muscle protein synthesis or reduced protein synthetic efficiencies. The aim of the present study was to characterise tissue composition of nucleic acids and rates of protein synthesis in non-cardiac tissues, such as liver, skeletal muscle (i.e., the Type I fibre-predominant soleus and Type II fibre-predominant plantaris), kidney, bone (tibia), skin and the gastrointestinal tract in a genetic model of hypertension (i.e., spontaneously hypertensive rats (SHRs), 15 weeks old) compared to their genetic aged-matched counterparts, i.e., normotensive Wistar-Kyoto (WKY) controls. Rates of protein synthesis were measured in vivo after injection with a flooding dose of L-[4-(3)H]phenylalanine. The results showed changed tissue wet weights (g per organ) for plantaris (+10%, P<0.05), liver (+25%, P<0.01), brain (-9%, P<0.01), jejunum (+39%, P<0.001) and tibia (+17%, P<0.001) in SHRs compared to WKY controls. Protein content (g or mg per organ) was increased in the liver (+32%, P<0. 01) and tibia (+37%, P<0.05). RNA contents (mg per organ) were increased in plantaris (+17%, P<0.01), liver (+22%, P<0.01) and jejunum (+11%, P<0.05). DNA (mg per organ) was increased in plantaris (+16%, P<0.025) and jejunum (+12%, P<0.025). The protein synthetic capacities (i.e., C(s), mg RNA/g protein) were higher in soleus (+41%, P<0.01) and plantaris (+6%, P<0.05) muscles of SHRs compared to WKYs, whereas values were lower in liver (-11%, P<0.01) and kidney (-6%, P<0.01) of SHRs compared to WKYs. The fractional rate of protein synthesis (i.e., k(s), the percentage of the protein pool renewed each day) was not significantly different for any of the tissues, though the rate of protein synthesis per unit RNA (i.e., k(RNA), mg protein/day per mg RNA) was reduced in the soleus (-24%, P<0.05) and the synthesis rate per unit DNA, i.e., k(DNA) (mg protein/day per mg DNA) was increased in the tibia (+31%, P<0.025). This is the first report of significant differences between indices of protein metabolism in extracardiac tissues in hypertension, which may reflect endocrine factors and/or the systemic influence of hypertension per se.
...
PMID:Non-cardiac nucleic acid composition and protein synthesis rates in hypertension: studies on the spontaneously hypertensive rat (SHR) model. 1069 31

GLUT4-null mice lacking the insulin-sensitive glucose transporter are not diabetic but do exhibit abnormalities in glucose and lipid metabolism. The most striking morphological consequence of ablating GLUT4 is cardiac hypertrophy. GLUT4-null hearts display characteristics of hypertrophy caused by hypertension. However, GLUT4-null mice have normal blood pressure and maintain a normal cardiac contractile protein profile. Unexpectedly, although they lack the predominant glucose transporter in the heart, GLUT4-null hearts transport glucose and synthesize glycogen at normal levels, but gene expression of rate-limiting enzymes involved in fatty acid oxidation is decreased. The GLUT4-null heart represents a unique model of hypertrophy that may be used to study the consequences of altered substrate utilization in normal and pathophysiological conditions.
...
PMID:Preservation of glucose metabolism in hypertrophic GLUT4-null hearts. 1089 71

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.
...
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

Changes in tissue protein synthesis in hypertension have usually been measured in vitro in heart from acutely hypertensive rats without consideration of changes in atrial or pulmonary tissue or changes occurring in long-standing hypertension. The objective of the study was to investigate the in vivo changes in cardiopulmonary protein synthesis in three different rat models of chronic hypertension. Hypertension in aortic constriction, the Goldblatt model, and the bromoethylamine model were induced in rats for 30 days. At the end of the experimental period, in vivo rates of protein synthesis were measured with a flooding dose of [3H]phenylalanine (a method which effectively considers precursor pools). Concomitant measurements included quantification of contractile protein and RNA and DNA contents. Indices of protein breakdown were also assessed by selective measurement of protease activities. At the end of 30 days, aortic constriction induced marked increases in protein contents of the left ventricle, septum, left atria, and lungs. Accompanying changes included concomitant increases in RNA and DNA contents. Left ventricular myofibrillary, sarcoplasmic, and stromal protein contents increased in the aortic constriction model. Less marked changes occurred in the Goldblatt model, though the left atria were not significantly affected. In contrast, the bromoethylamine model had no effect on the protein or RNA contents of any region. In all cardiac regions of all three models, fractional rates of protein synthesis were not significantly affected. However, protein synthesis increased in the lungs of both the Goldblatt and bromoethylamine models at 30 days. Protease activities were decreased in the left ventricles of all three models at 30 days, with lysosomal protease activities declining in the aortic constriction model and cytoplasmic protease activities declining in the other two models. The failure of chronic hypertension to increase ventricular synthesis rates may represent inherent limitations in the time frame for measuring protein synthesis in vivo. However, at earlier time points (i.e., 10 days), the aortic constriction model was characterized by marked increases in left ventricular and atrial protein contents, RNA contents, and fractional rates of protein synthesis. This was consistent with the supposition that, in acute phases of hypertrophy, rates of protein synthesis increase, whereas in established hypertrophy, synthesis rates remain unchanged or decrease. The applicability of the aortic constriction model was investigated by examining the effects of the angiotensin converting enzyme inhibitor lisinopril (5 mg/kg/day). After 30 days treatment, lisinopril impeded the increase in left ventricular mixed and myofibrillar proteins. This effect was accompanied by an apparent increase in protein synthesis. In conclusion, although all three chronic models are able to induce hypertension, varying degrees of hypertrophy develop, which are more pronounced in the aortic constriction model. Accompanying changes include hypertrophy in the atria, reduced rates of ventricular proteolytic activity, and altered rates of protein metabolism in the lungs.
...
PMID:In vivo protein synthetic rates of atrial, ventricular, and pulmonary tissue proteins in aortic constriction, goldblatt, and bromoethylamine models of hypertension. 1117 Jul 87

In recent years, the possibility that disorders of cardiac metabolism play a role in the mechanisms that lead to ventricular dilatation and dysfunction in heart failure has attracted much attention. Electron transport chain is constituted by a series of multimeric protein complexes, located in the inner mitochondrial membranes, whose genes are distributed over both nuclear and mitochondrial DNA. Its normal function is essential to provide the energy for cardiac function. Many studies have described abnormalities in mitochondrial DNA genes encoding for electron transport chain (ETC) in dilated cardiomyopathies. In some cases, heart failure is one more or less relevant symptom among other multisystem manifestations characteristic of mitochondrial encephalomyopathies, being heart failure imputable to a primary mitochondrial disease. In the case of idiopathic dilated cardiomyopathies (IDC), many mitochondrial abnormalities have also been described using hystological, biochemical or molecular studies. The importance of such findings is under debate. The great variability in the mitochondrial abnormalities described has prompted the proposal that mitochondrial dysfunction could be a secondary phenomenon in IDC, and not a primary one. Among other possible explanations for such findings, the presence of an increased oxidative damage due to a free radical excess has been postulated. In this setting, the dysfunction of ETC could be a consequence, but also a cause of the presence of an increased free radical damage. Independently of its origin, ETC dysfunction may contribute to the persistence and worsening of heart failure. If this hypothesis, still to be proven, was certain, the modulation of cardiac metabolism could be an interesting approach to treat IDC. The precise mechanisms that lead to ventricular dilatation and dysfunction in heart failure are still nowadays poorly understood. Circumstances such as cytotoxic insults, viral infections, immune abnormalities, contractile protein defects, ischemic factors and familial conditions have been thoroughly investigated [1]. It is possible that several mechanisms combine to produce the clinical syndrome of heart failure. In recent years the possibility that disorders of energy metabolism, either isolated or in combination with the other aforementioned factors, may play a role in the development of heart failure in susceptible patients has attracted much attention. The present paper reviews the current knowledge on mitochondrial function in the failing myocardium. We restrain our discussion to heart failure where an impaired inotropic state leads to a weakened systolic contraction (i.e. the so-called systolic heart failure). Idiopathic dilated cardiomyopathy (IDC) is the prototype of the conditions under discussion. Other circumstances where a defect in myocardial contraction is due to a chronic excessive work load (i.e., hypertension, valvular or congenital heart diseases), and states in which the principal abnormality involves impaired relaxation of the ventricle (i.e. diastolic heart failure), as well as mitochondrial defects outside the electron transport chain (i.e., defects in Krebs cycle or beta-oxidation of fatty acids) are only approached circumstantially.
...
PMID:Electron transport chain defects in heart failure. 1198 37

We examined whether adrenomedullin, a vasoactive peptide expressed in the heart, modulates the increase in blood pressure, changes in systolic and diastolic function, and left ventricular hypertrophy produced by long-term administration of ANG II or norepinephrine in rats. Subcutaneous administration of adrenomedullin (1.5 microg.kg(-1).h(-1)) for 1 wk inhibited the ANG II-induced (33.3 microg.kg(-1).h(-1) sc) increase in mean arterial pressure by 67% (P < 0.001) but had no effect of norepinephrine-induced (300 microg.kg(-1).h(-1) sc) hypertension. Adrenomedullin enhanced the ANG II-induced improvement in systolic function, resulting in a further 9% increase (P < 0.01) in the left ventricular ejection fraction and 19% increase (P < 0.05) in the left ventricular fractional shortening measured by echocardiography, meanwhile norepinephrine-induced changes in systolic function were remained unaffected. Adrenomedullin had no effect on ANG II- or norepinephrine-induced left ventricular hypertrophy or expression of hypertrophy-associated genes, including contractile protein and natriuretic peptide genes. The present study shows that adrenomedullin selectively suppressed the increase in blood pressure and augmented the improvement of systolic function induced by ANG II. Because adrenomedullin had no effects on ANG II- and norepinephrine-induced left ventricular hypertrophy, circulating adrenomedullin appears to act mainly as a regulator of vascular tone and cardiac function.
...
PMID:Adrenomedullin modulates hemodynamic and cardiac effects of angiotensin II in conscious rats. 1475 47

Cardiac hypertrophy in response to pressure overload is initially beneficial but eventually leads to heart failure, a major cause of morbidity and mortality in the Western countries. Although abnormalities in left ventricular (LV) diastolic filling are early features associated with pressure overload-induced LV hypertrophy, the molecular mechanisms regulating transition to diastolic heart failure are poorly understood. We analyzed global changes in gene expression in 12-, 16-, and 20-month-old spontaneously hypertensive rats (SHR) and their age-matched controls, Wistar Kyoto rats, using DNA microarrays. In SHR, a progressive LV hypertrophy was associated with increased expression of hypertrophy-associated genes including contractile protein and natriuretic peptide genes. Echocardiography indicated that 16-month-old SHR had features of diastolic dysfunction leading to diastolic failure at age 20 months without significant changes in LV systolic function. Comparison analysis revealed that the extracellular matrix genes strikingly dominated the list of altered genes after transition to the heart failure, whereas there was no major shift in gene expression patterns involved in calcium homeostasis and neurohumoral activation, as well as myofilament contractile and cytoskeletal proteins. The microarray analysis also revealed differential gene expression of several novel factors, such as thrombospondin-4 and matrix Gla protein, as well as unknown expressed sequence tags. Our data show that transition from LV hypertrophy to diastolic hypertensive heart failure is almost exclusively associated with progressive remodeling of the extracellular matrix and provide new insights into the pathogenesis of hypertrophy by suggesting existence of novel regulators of LV remodeling.
Hypertension 2005 May
PMID:Distinct upregulation of extracellular matrix genes in transition from hypertrophy to hypertensive heart failure. 1583 39


<< Previous 1 2 3 4 Next >>

---