Abstract
The SHR is characterized by an activated RAS, increased oxidative stress, endothelial dysfunction and impaired CG. Oligonucleotide microarray analyses were performed with SHR and WKY to gain insight into the molecular basis of CG impairment. The results demonstrated a fundamental difference in the overall gene expression pattern in collateral arteries compared to same animal controls. Downregulated collateral genes included AT1bR and angiotensinogen (AGT) while p22phox was upregulated in SHR control arteries relative to WKY (2.14+/− 0.50 vs 0.93+/−0.10). RT‐PCR confirmed the suppression of AGT in SHR and WKY (56+/−29% and 40+/−9%) and of AT1bR in SHR (42+/−9%). However, the AT1bR was upregulated in WKY collaterals (302+/−70%). Pretreatment with captopril, which we have previously shown to restore CG (Miller, AJP‐Heart, 292:2007), restored flow‐mediated NO production as assessed by in vivo periarterial NO measurement, prevented AT1R downregulation in collaterals (174+/−61%), and decreased p22phox expression. Losartan had no effect in SHR but prevented CG in WKY. Apocynin restored CG in SHR and had no effect in WKY. The results indicate an essential role for the AT1R in CG and suggest that the transcriptional regulation of this molecule during CG is modulated by the balance between oxidative stress and nitric oxide.Support: HL42898 and HL20605.
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