Role of Angiotension and CD36 Expression in Multiple Risk Factors for Atherosclerosis

目的：二氢吡啶类钙通道阻滞剂（CCB）可预防糖尿病心血管事件。血管紧张素II在导致血管疾病的病理生物学事件中起关键作用。本研究探讨了CCB和血管紧张素II受体阻滞剂对高血压心血管保护作用的长期影响。方法和结果：30周大的男性大冢朗埃文斯德德岛脂肪（OLETF）率，糖尿病模型血压升高，正常对照（Long Evans德岛大冢：LETO）大鼠喂食标准食物或含CCB阿折地平的食物，0.4 mg/g食物（每组n=15），持续2周。血管紧张素酶（ACE）mRNA在OLETF的肾皮质和髓质减少LETO大鼠相比，并进一步抑制阿折地平。OLETF组肾皮质盐皮质激素受体（MCR）mRNA表达高于LETO组，阿折地平组MCR mRNA表达显著降低。在46例高血压患者中，在缬沙坦40 ~ 160 mg/d治疗前和治疗后24周，测量臂踝间脉搏波传导速度（baPWV）。收缩压和舒张压分别从155±3降至140±3和从90±2降至82±2 mmHg。baPWV也从1853±49 cm/sec下降到1682 ±52 cm/sec.结论：我们证明阿折地平使糖尿病大鼠肾皮质MCR mRNA表达增加和肾ACE mRNA表达减少正常化。这是首次报道L型CCB可下调肾脏ACE和MCR mRNA的表达。我们的结论是，缬沙坦的治疗效果降低动脉僵硬度，无论基线血压。血压降低本身似乎并不能完全解释缬沙坦治疗对动脉硬化的益处。

OBJECTIVE : Diiihydropyridine calcium channel blockers (CCB) can prevent the CV events in diabetes. Angiotensin II plays a key role in pathobiological events that lead to vascular disease. The present study examined the long-term effects of CCB and angiotensin II receptor blocker on the cardiovascular protective effects in hypertension.METHODS and RESULTS : Thirty-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rates, a model of diabetes with elevated BP, and normal control (Long Evans Tokushima Otsuka : LETO) rats were fed standard chow or chow containing CCB azelnidipine, 0.4 mg/g food (n=15 in each group) for 2 weeks. Angiotensin enzyme (ACE) mRNA in both renal cortex and medulla of OLETF was reduced compared to LETO rats, and further suppressed by azelnidipine. The renal cortical mineralocorticoid receptor (MCR) mRNA in OLETF was higher than in LETO, and reduced significantly by azelnidipine. MCR mRNA in the renal medulla did not differ significantly between 2 strains, and was unaltered by azelnidipine in either strain.In 46 patients with hypertension, the pulse wave velocity between the brachium and ankle (baPWV) was measured before and 24 weeks after the treatment with valsartan 40 to 160 mg/day. Systolic and diastolic blood pressures were decreased from 155±3 to 140±3 and from 90±2 to 82±2 mmHg, respectively. The baPWV also decreased from 1853±49 cm/sec to 1682 ±52 cm/sec.CONCLUSION : We demonstrated that azelnidipine normalized the enhanced renal cortical expression of MCR mRNA and reduced renal ACE mRNA in diabetic rats. This is the first report providing that L-type CCB can down-regulated renal expression of ACE and MCR mRNA. We conclude that the treatment effect of valsartan reduces arterial stiffness regardless of baseline blood pressure. Blood pressure reduction alone does not appear to account entirely for the benefits of valsartan therapy on arterial stiffness.