The effects of circulating angiotensin II levels on vascular gene expression in normotensive rats

Abstract

Expression of mRNA for 84 genes implicated in hypertension was evaluated using pathway‐focused PCR arrays (SA Biosciences). Comparisons were made between salt‐sensitive (SS) vs. SS.13BN rats ± angiotensin II (ANG II) infusion (5 ng/kg/min) and in Sprague‐Dawley (SD) rats fed low salt diet (LS), high salt diet (HS), or HS + ANG II. In SS vs. SS.13BN, significant changes (p < 0.05) were observed for 21 genes with tendency for up‐ or down‐regulation (0.05 < p < 0.10) in 15 others. In SD, expression changes occurred in 16 genes, with trends towards up‐ or down‐regulation in 19 others. Angiotensin converting enzyme (ACE) expression was higher with elevated ANG II levels. Angiotensinogen was down‐regulated in SD rats fed HS but not in SS vs. SS.13BN. Several genes important to vasoreactivity showed altered expression with variations in circulating ANG II, including those important in the endothelin (ET) system, e.g., the ETB receptor was down‐regulated in HS vs. LS SD and in SS.13BN vs. SS. In SS.13BN, ET1 and endothelin converting enzyme 1 were down‐regulated vs. SS. The PGI2 receptor was down‐regulated in SS vs. SS.13BN and unchanged in SD. The B2 bradykinin receptor was up‐regulated in HS + ANG II vs. HS SD. These results indicate that plasma ANG II levels affect the expression of genes in cerebral arteries, but there are significant differences in the effect of ANG II on gene expression among strains. [NIH #HL65289 and HL92026].