ABSTRACT
The spontaneously hypertensive rat (SHR) is the most widely used animal model of essential hypertension and accompanying metabolic disturbances. Recent advances in sequencing of genomes of BN-Lx and SHR progenitors of the BXH/HXB recombinant inbred (RI) strains as well as accumulation of multiple data sets of intermediary phenotypes in the RI strains, including mRNA and microRNA abundance, quantitative metabolomics, proteomics, methylomics or histone modifications, will make it possible to systematically search for genetic variants involved in regulation of gene expression and in the etiology of complex pathophysiological traits. New advances in manipulation of the rat genome, including efficient transgenesis and gene targeting, will enable in vivo functional analyses of selected candidate genes to identify QTL at the molecular level or to provide insight into mechanisms whereby targeted genes affect pathophysiological traits in the SHR.
Subject(s)
Insulin Resistance/genetics , Metabolic Syndrome/genetics , Quantitative Trait Loci/genetics , Rats, Inbred SHR/genetics , Rats, Transgenic/genetics , Animals , Humans , Metabolic Syndrome/classification , Rats , Rats, Inbred SHR/classification , Species SpecificityABSTRACT
The spontaneously hypertensive stroke prone rat is best known as an inducible model of large artery stroke. Spontaneous strokes and stroke propensity in the spontaneously hypertensive stroke prone rat are less well characterized; however, could be relevant to human lacunar stroke. We systematically reviewed the literature to assess the brain tissue and small vessel pathology underlying the spontaneous strokes of the spontaneously hypertensive stroke prone rat. We searched systematically three online databases from 1970 to May 2010; excluded duplicates, reviews, and articles describing the consequences of induced middle cerebral artery occlusion or noncerebral pathology; and recorded data describing brain region and the vessels examined, number of animals, age, dietary salt intake, vascular and tissue abnormalities. Among 102 relevant studies, animals sacrificed after developing stroke-like symptoms displayed arteriolar wall thickening, subcortical lesions, enlarged perivascular spaces and cortical infarcts and hemorrhages. Histopathology, proteomics and imaging studies suggested that the changes not due simply to hypertension. There may be susceptibility to endothelial permeability increase that precedes arteriolar wall thickening, degeneration and perivascular tissue changes; systemic inflammation may also precede cerebrovascular changes. There were very few data on venules or tissue changes before hypertension. The spontaneously hypertensive stroke prone rat shows similar features to human lacunar stroke and may be a good spontaneous model of this complex human disorder. Further studies should focus on structural changes at early ages and genetics to identify factors that predispose to vascular and brain damage.
Subject(s)
Brain Ischemia/etiology , Disease Models, Animal , Hypertension/complications , Rats, Inbred SHR , Stroke, Lacunar/etiology , Stroke/etiology , Animals , Arterioles/pathology , Biomarkers , Blood Proteins/analysis , Blood-Brain Barrier , Brain/pathology , Brain Ischemia/pathology , Cerebral Arteries/pathology , Cerebral Hemorrhage/etiology , Cerebral Hemorrhage/pathology , Genetic Predisposition to Disease , Humans , Hypertension/genetics , Hypertension/pathology , Infarction, Middle Cerebral Artery/etiology , Infarction, Middle Cerebral Artery/pathology , Rats , Rats, Inbred SHR/classification , Rats, Inbred WKY , Research Design , Sodium Chloride, Dietary/toxicity , Species Specificity , Stroke/pathology , Stroke, Lacunar/pathology , Vasculitis/blood , Vasculitis/etiologyABSTRACT
The thrombotic tendency in two breeds of spontaneously hypertensive rats (SHRs) was assessed by inducing occlusive thrombosis in pial blood vessels using a helium-neon laser method. A prothrombotic state was observed in the SHR of one breed as compared to the corresponding control WKY, but not in the other. Circulating platelet and erythrocyte counts and haematocrit values were significantly negatively correlated in arterioles with the number of laser pulses, which is an index of the thrombotic tendency, suggesting that the prothrombotic state was partly dependent on the counts of blood components. However, there was no correlation between the measured blood parameters and prothrombotic state in venules. The difference observed in arterioles and venules might be due to their differential haemodynamics and endothelial properties. Prothrombotic state in the SHR of one breed would be partly due to the much higher difference in blood components from its corresponding control compared to the comparatively less difference in the other breed.
Subject(s)
Hypertension/genetics , Intracranial Embolism and Thrombosis/etiology , Rats, Inbred SHR/blood , Animals , Arterioles , Disease Susceptibility , Hematocrit , Hemodynamics , Hypertension/complications , Intracranial Embolism and Thrombosis/blood , Lasers/adverse effects , Male , Pia Mater/blood supply , Pia Mater/injuries , Rats , Rats, Inbred SHR/classification , Rats, Inbred WKY , VenulesABSTRACT
Repeated short oxygen exposition (60 min weekly, beginning at the 1st week of age up to the 18th week of age) induced in male spontaneously hypertensive rats (SHR) a diminished blood pressure rise. Oxygen exposed SHR had also lower heart rates than SHR without oxygen exposition. No significant differences were found in both these parameters in normotensive rats (WKY). Furthermore oxygen exposition decreased the erythrocyte sodium content of SHR.
