Increase Renal CYP2C23 Expression Using Thiazide Diuretics Attenuate the Progression of Cardiovascular Disease in Rat Model of Chronic Renal Failure

Abstract
Background: Cardiovascular diseases considered as major cause of morbidity and mortality in patients with chronic renal failure. CYP2C23 epoxygenases is one of CYP2C subfamily enzymes that expressed in the kidney. They convert arachidonic acid (AA) to Epoxyeicosatrienoic acids (EETs) which have an important role in regulation of cardiovascular function.
Aim of Study: Present study aimed to study the effect of indapamide on the expression of CYP2C23 and its impact on cardiovascular function in rat model of CRF.
Methods: Twenty four adult male albino rats were ran-domly divided to a sham operated, CRF which underwent 5/6 subtotal nephrectomy and CRF treated with indapamide 1mg/kg per day for 10 weeks.
Results: We demonstrated significant increase in systolic and diastolic blood pressure, deterioration in cardiac function (EF% and FS%) and impaired vascular reactivity in CRF group as compared to control group. Administration of inda-pamide significantly reverse the cardiovascular deterioration with increase in renal CYP2C23 expression and decrease cardiac NF-kB as compared to untreated group.
Conclusion: We concluded that indapamide prevent pro-gression of cardiovascular disease in rat model of chronic renal failure. We attributed this improvement to ability of indapamide to increase renal CYP2C23 expression which ameliorated oxidative stress and inflammation.