We performed
a DNA microarray analysis of the renal medulla and cortex from spontaneously hypertensive rats (SHRs),
stroke-prone SHRs (SHRSPs), and Wistar-Kyoto (WKY) rats to identify pivotal molecules in the kidney associated with the onset of
hypertension and found increased expression of
acyl-CoA oxidase 2 (Acox2)
mRNA. Real-time polymerase chain reaction revealed that Acox2
mRNA expression in the renal medulla and cortex of SHRs and SHRSPs was increased in comparison to WKY rats. These findings indicate that increased renal ACOX2 (an
enzyme that induces the β-oxidation of
fatty acids) is associated with the onset of
hypertension. Immunostaining of ACOX2 in the distal tubules from SHRs was stronger than that in the distal tubules from WKY rats. Western blot analysis showed increased expression of ACOX2
protein in renal medulla from SHRs. Regarding the overexpression of ACOX2, plasma levels of
phytanic acid in SHRs were significantly higher than those in WKY rats. There were no differences in other
short-chain fatty acids. Plasma
phytanic acid was affected by the gut microbiota through the conversion from
phytol by yeast in the intestinal tract. We compared the gut microbiota profile in three strains of 5-week-old rats by the terminal-restriction fragment length polymorphism method. The gut microbiota profile and ratio of Firmicutes/Bacteroides differed between SHRs and WKY rats. These findings suggest that the increased expression of ACOX2 in the kidney along with increases in plasma
phytanic acid and the altered gut microbiota may be involved in the oxidation in the kidney and the pathogenesis of
hypertension.