Neointimal hyperplasia and vasoreactivity are controlled by genetic elements on rat chromosome 3.

Neointimal hyperplasia (NIH) can lead to restenosis after clinical vascular interventions. NIH results from complex and poorly understood interactions between signaling cascades in the extracellular matrix and the disrupted endothelium, which lead to vessel occlusion. Quantitative trait loci (QTLs) were reported previously on rat chromosomes 3 and 6 through linkage analysis of postinjury NIH in midiliac arterial sections.

Epistatic genetic determinants of blood pressure and mortality in a salt-sensitive hypertension model.

Although genetic determinants protecting against the development of elevated blood pressure (BP) are well investigated, less is known regarding their impact on longevity. We concomitantly assessed genomic regions of rat chromosomes 3 and 7 (RNO3 and RNO7) carrying genetic determinants of BP without known epistasis, for their independent and combinatorial effects on BP and the presence of genetic determinants of survival using Dahl salt-sensitive (S) strains carrying congenic segments from Dahl salt-resistant (R) rats. Although congenic and bicongenic S.

Blood pressure and proteinuria effects of multiple quantitative trait loci on rat chromosome 9 that differentiate the spontaneously hypertensive rat from the Dahl salt-sensitive rat.

A blood pressure (BP) quantitative trait locus (QTL) was previously located within 117 kb on rat chromosome 9 (RNO9) using hypertensive Dahl salt-sensitive and normotensive Dahl salt-resistant rats. An independent study between two hypertensive rat strains, the Dahl salt-sensitive rat and the spontaneously hypertensive rat (SHR), also detected a QTL encompassing this 117 kb region. Dahl salt-sensitive alleles in both of these studies were associated with increased BP.

Congenic strains confirm aerobic running capacity quantitative trait loci on rat chromosome 16 and identify possible intermediate phenotypes.

We previously identified two inbred rat strains divergent for treadmill aerobic running capacity (ARC), the low-performing Copenhagen (COP) and the high-performing DA rats, and used an F(2)(COPxDA) population to identify ARC quantitative trait loci (QTLs) on rat chromosome 16 (RNO16) and the proximal portion of rat chromosome 3 (RNO3). Two congenic rat strains were bred to further investigate these ARC QTLs by introgressing RNO16 and the proximal portion of RNO3 from DA rats into the genetic background of COP rats and were named COP.DA(chr 16) and COP.

Substitution mapping in dahl rats identifies two distinct blood pressure quantitative trait loci within 1.12- and 1.25-mb intervals on chromosome 3.

Substitution mapping was used to refine the localization of blood pressure (BP) quantitative trait loci (QTL) within the congenic region of S.R-Edn3 rats located at the q terminus of rat chromosome 3 (RNO3). An F2(SxS.

Linkage analysis of neointimal hyperplasia and vascular wall transformation after balloon angioplasty.

Neointimal hyperplasia (NIH), a result of vascular injury, is due to the migration and proliferation of smooth muscle cells through the media and internal elastic lamina leading to vascular occlusion. We used a rat model to find the genetic regions controlling NIH after endothelial denudation in two divergent inbred strains of rats. The Brown Norway (BN) and spontaneously hypertensive rat (SHR) strains have a 2.

Gene expression profiling of the left ventricles in a rat model of intrinsic aerobic running capacity.

Our previous work found DA rats superior for intrinsic aerobic running capacity (ARC) and several cardiac function indexes compared with Copenhagen (COP) rats, and identified ARC quantitative trait loci (QTLs) on rat chromosomes 16 (RNO16) and 3 (RNO3). The purpose of this study was to use these inbred rat strains as a genetic substrate for differential cardiac gene expression to identify candidate genes for the observed ARC QTLs. RNA expression was examined globally in left ventricles of 15-wk-old DA, F1(COP x DA), and COP rats using microarrays to identify candidate genes for ARC QTLs.

Test of the principle of initial value in rat genetic models of exercise capacity.

An inverse relationship between initial level of physical capacity and the magnitude of response to training is termed the principle of initial value. We tested the operation of this principle under experimental conditions of minimal genetic and environmental variation. Inbred rat strains previously identified as genetic models of low [Copenhagen (COP)] and high [Dark Agouti (DA)] intrinsic (untrained) exercise capacity were trained for 8 wk on a treadmill using two disparate protocols: 1) a relative mode where each rat exercised daily according to its initial capacity, and 2) an absolute mode where both strains received the same amount of training independent of initial capacity.

Use of a panel of congenic strains to evaluate differentially expressed genes as candidate genes for blood pressure quantitative trait loci.

Candidate gene(s) for multiple blood pressure (BP) quantitative trait loci (QTL) were sought by analysis of differential gene expression patterns in the kidneys of a panel of eight congenic strains, each of which carries a different low-BP QTL allele with a genetic composition that is otherwise similar to that of the hypertensive Dahl salt-sensitive (S) rat strain. First, genes differentially expressed in the kidneys of one-month-old Dahl S and salt-resistant (R) rats were identified. Then, Northern filter hybridization was used to examine the expression patterns of these genes in a panel of congenic strains.

Functional genomics in rat models of hypertension: using differential expression and congenic strains to identify and evaluate candidate genes.

Hypertension is a leading contributor to cardiovascular diseases such as heart attack and stroke. Genetic and environmental factors contribute to the development of hypertension. Animal models have been developed to study the genetic contributions to blood pressure (BP) regulation and to identify chromosomal regions harboring candidate genes causative of differences in BP regulation (i.

A genome scan for Loci associated with aerobic running capacity in rats.

Aerobic capacity is a complex trait that defines the efficiency to use atmospheric oxygen as an electron acceptor in energy transfer. Copenhagen (COP) and DA inbred rat strains show a wide difference in a test for aerobic treadmill running and serve as contrasting genetic models for aerobic capacity. A genome scan was carried out on an F(2)(COP x DA) segregating population (n=224) to detect quantitative trait loci (QTLs) associated with aerobic running capacity.

Myocardial function in rat genetic models of low and high aerobic running capacity.

We recently evaluated treadmill aerobic running capacity in 11 inbred strains of rats and found that isolated working left ventricular function correlated (r = 0.86) with aerobic running capacity. Among these 11 strains the Buffalo (BUF) hearts produced the lowest and the DA hearts the highest isolated cardiac output.