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

目的：二氢吡啶钙通道阻滞剂(CCB)可预防糖尿病患者的心血管事件。血管紧张素II在导致血管疾病的病理生物学事件中起着关键作用。方法与结果：30周龄雄性OLETF(OLETF)大鼠，建立糖尿病血压升高模型，并与正常对照组(Long Evans Tokushima：LETO，Long Evans Tokushima Otsuka：Long Evans Tokushima：LETO)饲养2周，每组15只。与LETO大鼠相比，OLETF大鼠肾皮质和髓质血管紧张素酶(ACE)基因表达均降低，阿泽尼地平对其有进一步的抑制作用。OLETF组大鼠肾皮质糖皮质激素受体(MCR)的表达明显高于LETO组，而阿泽尼地平能显著降低MCR的表达。46例高血压病患者在服伐沙坦40~160 mg/d前和服药24周后，测量了肾髓质MCR基因的脉搏波速度(BaPWV)。收缩压由155±3降至140±3，舒张压由90±2降至82±2。BaPWV由1853±49 cm/s降至1682±52 cm/s。结论：阿泽尼地平可使糖尿病大鼠肾皮质MCR基因表达增强，ACE基因表达降低。这是首次报道L类中药能够下调肾脏血管紧张素转换酶和微血管紧张素受体的表达。我们得出结论，无论基线血压如何，valsartan的治疗效果都能降低动脉僵硬。仅仅降低血压似乎并不能完全解释valsartan治疗对动脉僵硬的好处。

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.