| Backgroud Hypertension is one of common cardiovascular diseases with about 130 million hypertensive patients in China so far. Hypertension-related complications, such as stroke, heart failure, and end-stage renal disease threaten the patients' life. The primary change in early hypertension was endothelial dysfunction, which should be a curse of main cardiovascular events. More and more evidence showed that oxidative stress plays a important role on the endothelial dysfunction in hypertension. How to reduce oxidative stress and improve endothelial function? This study was designed to solve those key questions. By the study, we could find a way to prevent the early changes of hypertension, which should be effective, safe, cheap, and available for long-term treatment. Objectives:1 . To observe oxidative stress, endothelial function, arterial remodeling in early hypertensive.2. To find out whether blood pressure lowering per se would improve impaired endothelial function.3. To find out whether antioxidants would reduce oxidative stress, and improve impaired endothelial function.4. To compare ACE inhibitor to antioxidants for ameliorating endothelial dysfunction.5. To evaluate two-dimensional and Doppler method for assessing endothelial function in clinic.Methods: This study include basic research and clinical research.Basic research:1. Build-up hypertensive model Renovascular hypertensive(RH) rats were be made by 2K1C. On the fourth week of surgery, RH rats were randomly divided into 4 groups, with 5 rats in each group: (1) RH rats untreated, (2) RH rats treated with diuretic+VC+VE for 8 weeks, (3)RH rats treated with diuretic for 8 weeks, (4) RH rats treated with perindopril for 8 weeks, respectively. Sham-operated rats underwent an identical surgical procedure, except 2K1C, as a control.2. Systolic blood pressure (SBP) was measured by the tail-cuff method at fourth, eighth, twelfth week, respectively.3. Blood was collected from orbit at fourth and twelfth week, respectively.4. To measure the resistance of the mesenteric vascular bed by Boric's protocol.5. To take aortic, heart, kidney, spleen for pathological study Aortic were washed with 0.9% NaC1 containing 0.16 mg/mL hearin to remove erythrocytes.6. To assay SOD, NO, NOS, iNOS, MDA, GSH-PX, OH in the aortic.7. To assay Vitamin C and E in the plasma.8. Pathological study All slices were stained by HE, and large arteries were stained with Resorcin-Fuchisin and Van Gisson. CMAS98A Artery Image Analysis System used for small or fine arteries of kidney and spleen.Clinical research:1. Subjects Healthy subjects and hypertensive patients with grade 1-2, exclude secondary hypertension, heart disease, stroke, hyperlipidemia, diabetes mellitus, liver dysfunction, kidney insufficiency and smoker. The patients were divided into 2 groups: (1) the patients treated with diuretic+VC+VE, (2) the patients treated with diuretic only. All patients needed to stop using antihypertensive drug for 2 weeksbefore recruitment.2. To examine brachial artery vasodilation using ultrasound with liyama's protocol.3. To assay TC, TG, LDL-C, HDL-C, blood sugar by OLYMPUS AU2700 machine at same day brachial artery vasodilation were examined.4. To assay Vit.C, Vit.E, SOD, Ox-LDL, ET, NO in the plasma before treatment and after the end of treatment for 12 weeks.Results:Basic research:1. After 2K1C surgery for 4 weeks, SBP in RH rat increased progressively, and significantly high at twelfth week comparing with sham-operated rats (194.00?2.94 vs 112.80?3.76 mmHg, p<0.01). Diuretic+VC+VE, diuretic and perindopril prevented from progression of blood pressure elevation. At the end of study, SBP was lower in diureticVC+VE-(118.00?16.43 mmHg), diuretic-(122.00?8.91 mmHg) and perindopril (128.00?1.51 mmHg) -treated groups. Compared with untreated controls, SBP was no difference significantly among them, whenas lower than that of RH group(p<0.01).2. Oxidative stress...
|
PDF Full Text Request