Effects of Hydrochlorothiazide and Indapamide the Expression of Cytochrome P_ (450) Hydroxylase in Liver, Kidney and Vascular Vessels in SHR

Back ground 20-HETE is one of magor metabolic products of arachidiomic and mediating by cytochrome P 450 hydroxylase(CYP4A). 20-HETE has been found to inhibit calcium activated K+ channels in vascular smooth muscle cell(VSMC), resulting in increases in intracellular Ca 2+ and vasoconstriction. Objective To investigate the effects of hydrochlorothiazide and indapamide on the blood pressure in spontaneous hypertensive rats (SHR) and the expression level of cytochrome P 450 hydroxylase in liver, kidney and vascular vessels. Methods Eighteen female SHRs were randomly divided into 3 groups (n6, each):control group; HCTZ10 mg·kg -1 ·d -1 group; indapamide (IND, 0.625 mg·kg -1 ·d -1 ) group. SBP was measured in pretreatment and each week of 4 weeks by given HCTZ and IND before sacrifice. After 4 week, CYP4A1 expression level in liver, kidney and aorta arteries of the three groups was studied using Western blot and RT-PCR analysis. Results Both HCTZ and IND decreased the SBP of SHRs significantly (P0.05). IND group showed more lower SBP than HCTZ group. HCTZ and IND increased the expression level of CYP4A1 (kidney 1.56±0.03;vascular 1.37±0.02). HCTZ increased the expression of CYP4A1 more pronouncedly compared with IND (kidney 1.36±0.01;vascular 1.25±0.02)(P0.05). Conclusion Both HCTZ and IND decreased the SBP of SHRs and increased the expression of CYP4A1.