Abstract
This study examined how hypertension related genes respond to dietary stress in the spontaneously hypertensive stroke prone rat (SHRSP) model. Weanling male SHRSP rats (n = 62) were fed a normo‐caloric diet supplemented with either 2% cholesterol (CHOL, wt/wt) or 0.2% oxidized cholesterol (oxCHOL, wt/wt) for 90 days. Blood pressure was recorded on days 30, 60, and 90 by femoral artery cannulation. RNA from hepatic and cardiac tissue were subjected to global gene expression using the oligonucleotide GeneChip microarray expression analysis. Selected inflammatory related genes were confirmed by Real Time‐PCR. Hepatic C‐reactive protein (CRP) mRNA levels increased by approximately 25% as a function of time and cholesterol in the diet. Pulse pressure increased, but did not differ with type of cholesterol consumed (CHOL, 47.2±3.2 and oxCHOL, 46.9±3.2 compared to control 34.03±3.2 mg/ml). This increase persisted through 90 days. Increase in vessel tone correlated (p蠄0.05) with a decline in HDL‐C by day 30. Moreover, the consumption of CHOL and oxCHOL markedly increased the expression of inflammation markers (vascular adhesion cell molecule 1 and chemokine receptors) in the aorta and heart. These data suggest that hypercholesterolemia precipitates inflammatory events leading to elevation in CRP, rise in pulse pressure, decrease in HDL‐C, and increase in vessel tone, leading to endothelial dysfunction.Grant Funding Source: Supported by NIH HL03389
Published Version
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