Effects of thiazide diuretics on expression of cytochrome P450 epoxgenase and angiotensin Ⅱ receptor type 1 in spontaneously hypertensive rats
摘要：
Objective To investigate the effects of hydrochlorothiazide (HCTZ) and indapamide on gene expression of cytochrome p450 (CYP) epoxgenase 2C11 and angiotensin Ⅱ receptor type 1 (AT 1) and to explore their molecular antihypertensive mechanisms. Methods Spontaneous hypertensive rats (SHR) were divided randomly into three groups and administered orally once a day with HCTZ (10 mg/kg), indapamide (0.625 mg/kg) and vehicle, respectively. Then body weight, blood pressure and 24 h urine volume were observed. All animals were sacrificed at 4 weeks after treatment. Morphological change and levels of gene expression of CYP2C11 and AT 1 were determined in major organs (heart, liver, kidneys and aorta). Results Both HCTZ and indapamide can effectively reduce blood pressure in SHRs, and also, up-regulate the gene expression of CYP 2C11 at mRNA and protein levels and down-regulate AT 1, so that attenuate damages of heart and kidneys induced by hypertension. Conclusion Thiazide diuretics can reduce elevated blood pressure and prevent organ damage through up-regulating the gene expression of CYP epoxgenase and down-regulating AT 1.
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2004
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