Sex-specific effects of abdominal aortic constriction on renal cytochrome P450 enzymes and arachidonic acid metabolites in male and female rats

We previously showed that male rats develop more severe cardiac hypertrophy than female rats following abdominal aortic constriction (AAC) and highlighted corresponding changes in cardiac cytochrome P450 (CYP) enzymes and their arachidonic acid (AA) metabolites. In this study, we report sex-specific changes in renal CYP enzymes and AA metabolites after AAC. Kidneys were isolated from adult male and female Sprague-Dawley rats 5 weeks after sham or AAC surgeries. Renal CYP, lipoxygenase, and epoxide hydrolase enzyme levels were measured by PCR and Western blot, and renal microsomal formation of hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) was measured by liquid chromatography-tandem mass spectrometry. Protein levels of CYP2E1 and CYP4F were significantly elevated post-AAC only in female rats, paralleled by a significant increase in their respective metabolites, 19(R)-HETE and 20-HETE. On the other hand, CYP2C23 mRNA levels were significantly decreased only in male rats, with no significant decrease in EETs. Our findings indicate that renal CYP-mediated AA metabolism undergoes sex-specific reprogramming in response to cardiac pressure overload, which may contribute to the observed divergent cardiac remodeling. This research highlights the importance of the kidney-heart axis and supports the potential for sex-specific metabolic targets in the treatment of cardiovascular diseases.