Project description:We investigated morphometric structure and gene expression by microarray analysis in a small diameter artery, branch of the saphenous artery (a resistance artery), in representative models of renin-angiotensin system (RAS)-dependent and glucocorticoid hypertension, using the spontaneously hypertensive rat (SHR) and adrenocorticotropic hormone (ACTH)-induced hypertensive rat, respectively. Sixteen-week-old male Wistar-Kyoto (WKY) and age-matched spontaneously hypertensive rats (SHR) were used. Keywords: Comparison of global gene expression in resistance arteries of normotensive and genetically hypertensive rats and ACTH-treated rats.
Project description:Genomic analysis of control and collateral arteries was used to investigate mechanisms responsible for impaired collateral growth in the Spontaneously Hypertensive rat, an animal model of essential hypertension with increased oxidative and nitrosative stress and metabolic abnormalities. A fundamental difference was observed in the overall expression pattern in SHR vs WKY collaterals. Redox related genes with altered expression included cyba (the gene encoding p22phox), superoxide dismutase 3, and thioredoxin reductases 1 and 2. Cystatin C, hevin, angiotensinogen, and the angiotensin type 1b receptor (AT1bR) had altered collateral expression that was confirmed by RT-PCR. These molecules are known to have significant roles in other types of arterial remodeling. Of specific interest was the AT1bR which exhibited up-regulation in WKY collaterals, but down-regulation in SHR. A remarkable increase in AT1R protein was observed in WKY but not SHR collaterals. Pharmacological blockade of the AT1R with losartan prevented collateral luminal expansion in WKY. In SHR, captopril restored redox status assessed by cyba expression and nitric oxide concentration, prevented collateral AT1bR down-regulation and re-established the capacity for collateral growth. These results indicate that redox-status significantly alters flow-mediated transcriptional regulation and demonstrate that increased flow-related expression/activation of the AT1R is required for normal collateral luminal expansion but is altered by chronic oxidative and/or nitrosative stress in hypertensive rats. Keywords: gene expression two strains: two vessel types
Project description:We investigated morphometric structure and gene expression by microarray analysis in a small diameter artery, branch of the saphenous artery (a resistance artery), in representative models of renin-angiotensin system (RAS)-dependent and glucocorticoid hypertension, using the spontaneously hypertensive rat (SHR) and adrenocorticotropic hormone (ACTH)-induced hypertensive rat, respectively. Sixteen-week-old male Wistar-Kyoto (WKY) and age-matched spontaneously hypertensive rats (SHR) were used. Experiment Overall Design: There were 3 experimental groups: Group 1: 16-week male Wistar-Kyoto rats; Group 2: 16-week male Wistar-Kyoto rats treated with ACTH (0.1mg/kg/day) subcutaneously, for 4 weeks prior to sampling (i.e. during weeks 12-16 of life) ; Group3: 16-week male SHR (spontaneously hypertensive) rats. There were 3 replicate hybridizations in each experimental group. Due to the low yield of total RNA obtained from the arterial sections, each replicate was composed of RNA pooled from 2-3 different rats.