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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Models of right ventricular hypertrophy in rats have been created and characterized: Daily injections of triiodothyronine, irradiation of the lung in Brown-Norway rats, chronic myocardial infarction, and pulmonary artery stenosis. A new Millar ultraminature catheter pressure transducer designed for right heart catheterization allowed the measurement of right ventricular function. All models were characterized by an increase in right ventricular systolic pressure, by an elevation in the RNA/DNA ratio in the right ventricle, and by an increase in the right ventricular weight/body weight ratio. Myocytes isolated from the right ventricle 4 weeks after coronary artery ligation had a greater volume and cross sectional area. Similar results were obtained 14 days after pulmonary artery stenosis. In this model, the effect of angiotensin converting enzyme inhibition with ramipril (1 mg/kg, daily) was examined. The increase in right ventricular systolic pressure from 35 +/- 2 mm Hg to 61 +/- 4 mm Hg (without ramipril) was not influenced by ramipril (63 +/- 4 mm Hg), neither was the elevation of right ventricular weight. However, the increase in cell volume and cross-sectional area of myocytes isolated from the right ventricle was less pronounced in the ramipril-treated group (+27% compared to +58% in untreated animals). Thus, angiotensin converting enzyme inhibition with ramipril altered the hypertrophic response at the cellular level.
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PMID:[Right ventricular hypertrophy in rats: effect of ACE inhibitors]. 183 Sep 10

Using a special Millar ultraminiature catheter pressure transducer, right ventricular functional parameters were measured in anesthetized, closed-chest rats under control conditions, during acute pulmonary hypertension and after induction of right ventricular hypertrophy. Acute i.v. infusion of noradrenaline and a brief period of hypoxia in female Sprague-Dawley rats elicited a marked increase in right ventricular systolic pressure (RVSP) and in the maximal rate of rise in right ventricular pressure (RV dp/dtmax). After 3 and 16 days of daily administrations of triiodothyronine in female Sprague-Dawley rats, all right ventricular hemodynamic parameters were enhanced along with the increase in left ventricular function. The right and left ventricles were hypertrophied, and cardiac output was increased. After 40 and 45 days subsequent to bilateral thorax irradiation of male Brown-Norway rats, RVSP and RV dp/dtmax were increased, the right ventricle was hypertrophied, while the left ventricle did not exhibit appreciable hemodynamic or morphologic alterations. Cardiac output was depressed. Thus, these two experimental models differ considerably as to the mechanism and time course of the development of right ventricular hypertrophy as well as to the participation of the left ventricle and the involvement of volume overload.
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PMID:Right heart catheterization in rats with pulmonary hypertension and right ventricular hypertrophy. 245 97

Left ventricular hypertrophy remains a significant clinical problem and a predictor of fatal outcome in hypertension. Blood pressure per se and environmental modifiers including stress affect cardiac mass. Heat shock proteins are involved in the stress response as well as in the regulation of cardiac growth and cytoprotection. The present study evaluates heat shock protein 27 as a locus marker or candidate gene of cardiac hypertrophy in hypertension. The spontaneously hypertensive rat allele of heat shock protein 27 was associated with about a 6% increase in relative left ventricular weight (P = .0112) in 30 recombinant inbred strains from crosses of Brown Norway and spontaneously hypertensive rats. In 336 F2 crosses of spontaneously hypertensive and Wistar-Kyoto rats, the hypertensive allele was dominant and cosegregated with a similar 6% increase in the ratio of left ventricular weight to body weight (P = .0058) in rats fed a normal salt diet, but its contribution to left ventricular weight decreased in rats kept on a high salt diet. The contribution of the heat shock protein 27 allele was independent of blood pressure. We suggest that heat shock protein 27 represents a candidate gene/locus marker of cardiac hypertrophy in hypertension.
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PMID:HSP27 locus cosegregates with left ventricular mass independently of blood pressure. 895 7

This review deals with the largest set of rat recombinant inbred (RI) strains and summarizes past and recent accomplishments with this platform for genetic mapping and analyses of divergent and complex traits. This strain, derived by crossing the spontaneously hypertensive rat, SHR/Ola, with a Brown Norway congenic, BN-Lx, carrying polydactyly-luxate syndrome, is referred to as HXB/BXH. The RI strain set has been used for linkage and association studies to identify quantitative trait loci for numerous cardiovascular phenotypes, including arterial pressure, stress-elicited heart rate, and pressor response, and metabolic traits, including insulin resistance, dyslipidemia and glucose handling, and left ventricular hypertrophy. The strain's utility has been enhanced with development of a new framework marker-based map and strain distribution patterns of polymorphic markers. Quantitative trait loci for behavioral traits mapped include loci for startle motor response and habituation, anxiety and locomotion traits associated with elevated plus maze, and conditioned taste aversion. The polydactyly-luxate syndrome Lx mutation has allowed the study of alleles important to limb development and malformation phenotypes as well as teratogens. The RI strains have guided development of numerous congenic strains to test locus assignments and to study the effect of genetic background. Although these strains were originally developed to aid in studies of rat genetic hypertension and morphogenetic abnormalities, this rodent platform has been shown to be equally powerful for a wide spectrum of traits and endophenotypes. These strains provide a ready and available vehicle for many physiological and pharmacological studies.
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PMID:Genetic Models in Applied Physiology. HXB/BXH rat recombinant inbred strain platform: a newly enhanced tool for cardiovascular, behavioral, and developmental genetics and genomics. 1273 93

To determine circulating angiotensin-(1-7) [Ang-(1,7)] levels in rats with different angiotensin converting enzyme (ACE) genotypes and to evaluate the effect of hypertension on levels of this heptapeptide, plasma levels of angiotensin II (Ang II) and Ang-(1-7) were determined by HPLC and radioimmunoassay in (a) normotensive F0 and F2 homozygous Brown Norway (BN; with high ACE) or Lewis (with low ACE) rats and (b) in hypertensive F2 homozygous male rats (Goldblatt model). Genotypes were characterized by PCR and plasma ACE activity measured by fluorimetry. Plasma ACE activity was 2-fold higher (p < 0.05) in homozygous BN compared to homozygous Lewis groups. In the Goldblatt groups, a similar degree of hypertension and left ventricular hypertrophy was observed in rats with both genotypes. Plasma Ang II levels were between 300-400% higher (p < 0.05) in the BN than in the Lewis rats, without increment in the hypertensive animals. Plasma Ang-(1-7) levels were 75-87% lower in the BN rats (p < 0.05) and they were significantly higher (p < 0.05) in the hypertensive rats from both genotypes. Plasma levels of Ang II and Ang-(1-7) levels were inversely correlated in the normotensive rats (r = -0.64; p < 0.001), but not in the hypertensive animals. We conclude that there is an inverse relationship between circulating levels of Ang II and Ang-(1-7) in rats determined by the ACE gene polymorphism. This inverse relation is due to genetically determined higher ACE activity. Besides, plasma levels of Ang-(1-7) increase in renovascular hypertension.
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PMID:Effect of hypertension on angiotensin-(1-7) levels in rats with different angiotensin-I converting enzyme polymorphism. 1622 62

Aging is associated with left ventricular hypertrophy, dilatation, and fibrosis of the heart. The Fischer 344/Brown Norway F1 (F344/BNF1) rat is recommended for age-related studies by the National Institutes on Aging because this hybrid rat lives longer and has a lower rate of pathological conditions than inbred rats. However, little is known about age-associated changes in cardiac and aortic function and structure in this model. This study evaluated age-related cardiac changes in male F344/BNF1 rats using ECHO, gross, and microscopic examinations. Rats aged 6-, 30-, and 36-mo were anesthetized and two-dimensional ECHO measurements, two-dimensional guided M-mode, Doppler M-mode, and other recordings from parasternal long- and short-axis views were obtained using a Phillips 5500 ECHO system with a 12 megahertz transducer. Hearts and aortas from sacrificed rats were evaluated grossly and microscopically. The ECHO studies revealed persistent cardiac arrhythmias (chiefly PVCs) in 72% (13/18) of 36-mo rats, 10% (1/10) of 30-mo rats, and none in 6-mo rats (0/16). Gross and microscopic studies showed left ventricular (LV) dilatation, borderline to mild hypertrophy, and areas of fibrosis that were common in 36-mo rats, less evident in 30-mo rats, and absent in 6-mo rats. Aging was associated with mild to moderate decreases of LV diastolic and systolic function. Thus, male F344/BN F1 rats demonstrated progressive age-related (a) decline in cardiac function (diastolic and systolic indices), (b) LV structural changes (chamber dimensions, volumes, and wall thicknesses), and (c) persistent arrhythmias. These changes are consistent with those in humans. The noninvasive ECHO technique offers a means to monitor serial age-related cardiac failure and therapeutic responses in the same rats over designated time intervals.
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PMID:Age-associated changes in hearts of male Fischer 344/Brown Norway F1 rats. 1712 29

Determination of the genetic factors that control the progression of left ventricular hypertrophy (LVH) to heart failure has been difficult despite extensive study in animal models. Here we have characterized a consomic rat model of LVH resulting from the introgression of chromosome 16 from the normotensive Brown Norway (BN) rat onto the genetic background of the Dahl salt-sensitive (SS/Mcwi) rat by marker assisted breeding. The SS-16BN/Mcwi consomic rats are normotensive but display LVH equivalent to the hypertensive SS/Mcwi rats at early ages. In this study we tracked the development of LVH by echocardiography and analyzed changes in cardiac function and morphology with aging in the SS-16BN/Mcwi, SS/Mcwi, and BN to determine if the consomic SS-16BN/Mcwi was a model of hypertrophic cardiomyopathy (HCM). Aging SS-16BN/Mcwi rats showed no evidence of heart failure or impaired cardiac function upon extensive analysis of left ventricle function by echocardiography and pressure-volume relationships, while their parental SS/Mcwi experienced deterioration in function between 18 and 36 wk of age. In addition aging SS-16BN/Mcwi did not exhibit tissue remodeling common to pathological hypertrophy and HCM such as increased fibrosis and reduced capillary density in the myocardium. In fact, SS-16BN/Mcwi were better protected from developing LV fibrosis with age than either the hypertensive SS/Mcwi or normotensive BN parental strains. This suggests that a gene or genes on chromosome 16 may be involved with both blood pressure regulation and preservation of cardiac function with aging.
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PMID:Substitution of Brown Norway chromosome 16 preserves cardiac function with aging in a salt-sensitive Dahl consomic rat. 1894 Aug 98

The spontaneously hypertensive rat (SHR) is the most widely used animal model of essential hypertension and accompanying metabolic disturbances. In this model, the use of whole genome sequencing and gene expression profiling techniques, linkage and correlation analyses in recombinant inbred strains, and in vitro and in vivo functional studies in congenic and transgenic lines has recently enabled molecular identification of quantitative trait loci (QTLs) relevant to the metabolic syndrome: (1) a deletion variant in Cd36 (fatty acid translocase) responsible for QTLs on chromosome 4 associated with dyslipidemia, insulin resistance and hypertension, (2) mutated Srebf1 (sterol regulatory element binding factor 1) as a QTL on chromosome 10 influencing dietary-induced changes in hepatic cholesterol levels, and (3) Ogn (osteoglycin) as a QTL on chromosome 17 associated with left ventricular hypertrophy. In addition, selective replacement of the mitochondrial genome of the SHR with the mitochondrial genome of the Brown Norway rat influenced several major metabolic risk factors for type 2 diabetes and provided evidence that spontaneous variation in the mitochondrial genome per se can promote systemic metabolic disturbances relevant to the pathogenesis of metabolic syndrome. Owing to recent progress in the development of rat genomic resources, the pace of QTL identification and discovery of new disease mechanisms can be expected to accelerate in the near future.
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PMID:Use of rat genomics for investigating the metabolic syndrome. 2001 49

The SS-16(BN)/Mcwi consomic rat was produced by the introgression of chromosome 16 from the Brown Norway (BN/NHsdMcwi) rat onto the genetic background of the Dahl salt-sensitive (SS/Mcwi) rat by marker-assisted breeding. We have previously shown that the normotensive SS-16(BN)/Mcwi consomic strain is better protected from developing left ventricular dysfunction and fibrosis with aging than the hypertensive SS/Mcwi parental strain; however, the mechanism of this protection was not clear since the SS-16(BN)/Mcwi had both lowered blood pressure and an altered genetic background compared with SS/Mcwi. Microarray analysis of SS-16(BN)/Mcwi and SS/Mcwi left ventricle tissue and subsequent protein pathway analysis were used to identify alterations in gene expression in signaling pathways involved with the observed cardioprotection on the SS background. The SS-16(BN)/Mcwi rats exhibited much higher mRNA levels of expression of transcription factor JunD, a gene found on chromosome 16. Additionally, high levels of differential gene expression were found in pathways involved with angiogenesis, oxidative stress, and growth factor signaling. We tested the physiological relevance of these pathways by experimentally determining the responsiveness of neonatal cardiomyocytes to factors from identified pathways and found that cells isolated from SS-16(BN)/Mcwi rats had a greater growth response to epidermal growth factor and endothelin-1 than those from parental SS/Mcwi. We also demonstrate that the SS-16(BN)/Mcwi is better protected from developing fibrosis with surgically elevated afterload than other normotensive strains, indicating that gene-gene interactions resulting from BN chromosomal substitution confer specific cardioprotection. When combined with our previous findings, these data suggest that that SS-16(BN)/Mcwi may have an increased angiogenic potential and better protection from oxidative stress than the parental SS/Mcwi strain. Additionally, the early transient idiopathic left ventricular hypertrophy in the SS-16(BN)/Mcwi may be related to altered myocyte sensitivity to growth factors.
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PMID:Mechanisms of cardioprotection resulting from Brown Norway chromosome 16 substitution in the salt-sensitive Dahl rat. 2275 22

The spontaneously hypertensive rat (SHR) is the most widely used animal model of essential hypertension and left ventricular hypertrophy. Catecholamines play an important role in the pathogenesis of both essential hypertension in humans and in the SHR. Recently, we obtained evidence that the SHR harbors a variant in the gene for dopamine beta hydroxylase (Dbh) that is associated with reduced adrenal expression of Dbh mRNA and reduced DBH enzymatic activity which correlated negatively with blood pressure. In the current study, we used a transgenic experiment to test the hypothesis that reduced Dbh expression predisposes the SHR to hypertension and that augmentation of Dbh expression would reduce blood pressure. We derived 2 new transgenic SHR-Dbh lines expressing Dbh cDNA under control of the Brown Norway (BN) wild type promoter. We found modestly increased adrenal expression of Dbh in transgenic rats versus SHR non-transgenic controls that was associated with reduced adrenal levels of dopamine and increased plasma levels of norepinephrine and epinephrine. The observed changes in catecholamine metabolism were associated with increased blood pressure and left ventricular mass in both transgenic lines. We did not observe any consistent changes in brainstem levels of catecholamines or of mRNA levels of Dbh in the transgenic strains. Contrary to our initial expections, these findings are consistent with the possibility that genetically determined decreases in adrenal expression and activity of DBH do not represent primary determinants of increased blood pressure in the SHR model.
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PMID:Effects of transgenic expression of dopamine beta hydroxylase (Dbh) gene on blood pressure in spontaneously hypertensive rats. 2795 76


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