Abstract

BackgroundArachidonic acid (AA) is oxidized by cytochrome P450s (CYPs) to form epoxyeicosatrienoic acids (EETs), compounds that modulate ion transport, gene expression, and vasorelaxation. Both CYP2Cs and CYP2Js are involved in kidney EET epoxidation.MethodsIn this study, we used a CYP2C11-null rat model to explore the in vivo effects of CYP2C11 on vasorelaxation. For 2 months, CYP2C11-null and wild-type (WT) Sprague-Dawley rats were either fed normal lab (0.3% (w/w) sodium chloride) or high-salt (8% (w/w) sodium chloride) diets. Subsequently, an invasive method was used to determine blood pressure. Next, western blots, quantitative PCR, and immunohistochemistry were used to determine renal expression of CYPs involved in AA metabolism.ResultsAmong CYP2C11-null rats, a high-salt diet (females: 156.79 ± 15.89 mm Hg, males: 130.25 ± 16.76 mm Hg, n = 10) resulted in significantly higher blood pressure than a normal diet (females: 118.05 ± 8.43 mm Hg, P < 0.01; males: 115.15 ± 11.45 mm Hg, P < 0.05, n = 10). Compared with WT rats under the high-salt diet, western blots showed that CYP2C11-null rats had higher renal expression of CYP2J2 and CYP4A. This was consistent with the results of immunohistochemistry and the qPCR, respectively. The two rat strains did not differ in the renal expression of CYP2C23 or CYP2C24.ConclusionOur findings suggested that CYP2C11 plays an important role in lowering blood pressure under the challenge of a high-salt diet.

Highlights

  • Hypertension is a common condition that can lead to ischemic heart disease, cerebrovascular disease, and chronic kidney disease (Collins et al, 1990; Van Gaal, Mertens & De Block, 2006; Wright, 2002)

  • High-salt diets elevated blood pressure in CYP2C11-null rats Under a normal lab diet, CYP2C11-null and WT rats did not differ in blood pressure (n 1⁄4 10)

  • Western blots of CYP2J2 and CYP4A in rat kidney microsomes Under the normal diet, the expression of CYP2J2 in CYP2C11-null male rats was significantly higher than that in WT male rats

Read more

Summary

Introduction

Hypertension is a common condition that can lead to ischemic heart disease, cerebrovascular disease, and chronic kidney disease (Collins et al, 1990; Van Gaal, Mertens & De Block, 2006; Wright, 2002). CYP2C11 played a significant role in down-regulating rat blood pressure under the challenge of a high-salt diet. Arachidonic acid (AA) is oxidized by cytochrome P450s (CYPs) to form epoxyeicosatrienoic acids (EETs), compounds that modulate ion transport, gene expression, and vasorelaxation. Both CYP2Cs and CYP2Js are involved in kidney EET epoxidation. Compared with WT rats under the high-salt diet, western blots showed that CYP2C11-null rats had higher renal expression of CYP2J2 and CYP4A. This was consistent with the results of immunohistochemistry and the qPCR, respectively. Conclusion: Our findings suggested that CYP2C11 plays an important role in lowering blood pressure under the challenge of a high-salt diet

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call