替米沙坦对高血压伴有胰岛素抵抗及左室肥厚的影响

目的:探讨替米沙坦对非糖尿病高血压病患者伴有胰岛素抵抗及左室肥厚的影响。方法:替米沙坦治疗非糖尿病高血压病患者46例,治疗前后测定基础血压、空腹血糖(FBG)、空腹胰岛素(FINS)水平。以稳态模型(homa model)公式计算胰岛素抵抗(IR),并行超声心动图检查。结果:治疗后收缩压由治疗前的(167±31)mmHg降至(128±19)mmHg;舒张压由治疗前的(101±11)mmHg降至(78±9)mmHg。空腹胰岛素水平、胰岛素抵抗指数均较治疗前显著下降(P<0.05),室间隔厚度、左心室后壁厚度、左心室心肌质量和左心室质量指数均明显改善(P<0.05)。结论:替米沙坦能减轻高血压患者的左室重构,这可能与改善胰岛素抵抗有关。     

Losartan: a selective angiotensin II type 1 (AT1) receptor antagonist for the treatment of heart failure

Losartan (COZAARΟχιρχ^?) is the prototype of a new class of potent and selective angiotensin II (AII) type 1 (AT₁) receptor antagonists with the largest published preclinical and clinical data base. Since all of the AII antagonists are selective for the AT₁ receptor, these drugs should exhibit similar cardiovascular effects. However, since the pharmacokinetic/pharmacodynamic profiles of these agents and their degree of affinity for the AT₁ receptor differ, it is likely that differences in clinical profiles between these drugs exist and will require investigation. Losartan (parent compound), has moderate affinity for the AT₁ receptor (competitive inhibition). Losartan is well-absorbed orally as an active drug and is rapidly converted via oxidation in the human liver to a more potent metabolite (designated E3174) with an affinity 20- to 30-times greater for the AT₁ receptor (non-competitive inhibition). E3174 has a half-life of 6 - 9 h; elimination is via renal and hepatic routes. Antihypertensive and, in heart failure patients, haemodynamic activity is observed over a 24 h period with once daily dosing. Over 6 million patients have been treated for hypertension with continued excellent tolerability. Clinical experience in heart failure is growing, and recent data suggest an improved survival with losartan versus captopril, a drug from the angiotensin-converting-enzyme inhibitor class with proven benefit in this population. The current comprehensive losartan clinical end-point programme (4 large scale morbidity/mortality trials) should provide evidence regarding the efficacy of direct blockade of the AT₁ receptor with losartan compared to standard therapy: 1) The Losartan Heart Failure Survival Study - ELITE II, 2) The Losartan Post-Myocardial Infarction Survival Study - OPTIMAAL, 3) The Losartan Hypertension Survival Study - LIFE and 4) The Losartan Renal Protection Study - RENAAL.     

补肾通脉方对Ⅱ型糖尿病大鼠骨骼肌胰岛素受体表达的影响

目的：探讨补肾通脉方对Ⅱ型糖尿病大鼠骨骼肌胰岛素受体表达的影响。方法：采用小剂量链脲佐菌素加高热量饲养方法建立Wistar大鼠Ⅱ型糖尿病模型，并随机分为模型组、中药组及西药组(分别用补肾通脉方和二甲双胍干预8周)，另设正常组(喂以普通饲料)；检测骨骼肌组织中三酰甘油(mTG)含量；以逆转录聚合酶链式反应(RT-PCR)检测骨骼肌组织胰岛素受体(InsR)mRNA的表达水平。结果：与正常组相比，模型组骨骼肌组织mTG水平明显升高(P＜0.01)，而InsR mRNA表达显著减少(P＜0．01)；与模型组比较，中药组骨骼肌组织mTG水平显著降低(P＜0．01)，InsR mRNA表达则显著增提高(P＜0.01)。结论：补肾通脉方改善胰岛素抵抗的作用机制可能与其上调Ⅱ型糖尿病大鼠骨骼肌组织InsR mRNA表达水平有关。     

Regulation of angiotensin-(1-7) and angiotensin II type 1 receptor by telmisartan and losartan in adriamycin-induced rat heart failure

Aim:

To investigate the possible effects of telmisartan and losartan on cardiac function in adriamycin (ADR)-induced heart failure in rats, and to explore the changes in plasma level of angiotensin-(1–7)[Ang-(1–7)] and myocardial expression of angiotensin II type 1/2 receptors (AT1R / AT2R) and Mas receptor caused by the two drugs.

Methods:

Male Sprague-Dawley rats were randomly divided into 4 groups: the control group, ADR-treated heart failure group (ADR-HF), telmisartan plus ADR-treated group (Tel+ADR) and losartan plus ADR-treated group (Los+ADR). ADR was administrated (2.5 mg/kg, ip, 6 times in 2 weeks). The rats in the Tel+ADR and Los+ADR groups were treated orally with telmisartan (10 mg/kg daily po) and losartan (30 mg/kg daily), respectively, for 6 weeks. The plasma level of Ang-(1–7) was determined using ELISA. The mRNA and protein expression of myocardial Mas receptor, AT₁R and AT₂R were measured using RT-PCR and Western blotting, respectively.

Results:

ADR significantly reduced the plasma level of Ang-(1–7) and the expression of myocardial Mas receptor and myocardial AT₂R, while significantly increased the expression of myocardial AT1R. Treatment with telmisartan and losartan effectively increased the plasma level of Ang-(1–7) and suppressed myocardial AT1R expression, but did not influence the expression of Mas receptor and AT₂R.

Conclusion:

The protective effects of telmisartan and losartan in ADR-induced heart failure may be partially due to regulation of circulating Ang-(1–7) and myocardial AT1R expression.     

单纯性肥胖及2型糖尿病儿童胰岛素受体底物-1的研究

目的:探讨单纯性肥胖及2型糖尿病儿童胰岛素受体底物-1(IRS-1)表达的改变。方法:对20例单纯性肥胖儿童,20例2型糖尿病儿童及20例对照组儿童,采用细胞免疫技术进行白细胞染色,运用图像分析软件计算光密度值,从而定量分析白细胞中IRS-1的含量变化。结果:肥胖组、2型糖尿病组白细胞中IRS-1表达下降,且与对照组相比有统计学意义(P<0.05)。结论:肥胖组、2型糖尿病组白细胞中IRS-1表达下降,与对照组相比有统计学意义(P<0.05),提示肥胖组与2型糖尿病组儿童胰岛素信号传递中受体后作用的关键底物缺陷,影响了胰岛作用的发挥。提示IRS-1与胰岛素抵抗有关,有利于进一步理解2型糖尿病的发病机制,指导临床治疗。     

Effect of adrenotensin on cell proliferation is mediated by angiotensin II in cultured rat mesangial cells

Aim： Both adrenomedullin （ADM） and adrenotensin （ADT） are derived from the same propeptide precursor, and both act as circulating hormones and local paracrine mediators with multiple biological activities. Compared with ADM, little is known about how ADT achieves its functions. In the present study, we investigated the effect of ADT on cell proliferation and transforming growth factor-β（TGF-β） secretion in cultured renal mesangial cells （MCs） and determined whether angiotensin II （Ang II） was involved in mediating this process. Methods： Cell proliferation was measured by bromodeoxyuridine （BrdU） incorporation assay, Ang II levels were assayed using an enzyme immunoassay, and real time PCR was used to measure Ang II type 1 （AT1） receptor, Ang II type 2 （AT2） receptor, angiotensinogen （AGT）, renin, angiotensin converting enzyme （ACE） and TGF-β1 mRNA levels. TGF-β1 and collagen type IV protein levels in cell media were measured using enzyme-linked immunoassays. Results： ADT treatment induced cell proliferation in a concentration-dependent manner; it also increased the levels of TGF-β1 mRNA and protein as well as collagen type IV excretion by cultured MCs. ADT treatment increased renin and AGT mRNAs as well as Ang II protein, but did not affect the ACE mRNA level. ADT up-regulated angiotensin AT1 receptor mRNA, but not that of the AT2 receptor. The angiotensin AT1 receptor antagonist Iosartan blocked the effects of ADT-induced cell proliferation, TGF-β1 and collagen type IV synthesis and secretion. Conclusion： ADT has a stimulating role in cell proliferation in cultured MCs. Increases in the levels of Ang II and the AT1 receptor after ADT treatment mediate the stimulating effects of ADT on cell proliferation and extracellular matrix synthesis and secretion.     

成纤维细胞生长因子-21改善胰岛素抵抗肝细胞对葡萄糖的吸收及机制

目的建立正常人肝细胞(HL-7702)胰岛素抵抗(in-sulin resistance,IR)模型,探讨成纤维细胞生长因子-21(FGF-21)对胰岛素抵抗的改善作用及其机制。方法培养HL-7702细胞,利用高浓度胰岛素和地塞米松(dexametha-sone,DEX)诱导IR模型。GOD-POD试剂盒测定细胞葡萄糖消耗量,Western blot检测GLUT1和磷酸化ERK1/2表达水平。结果 FGF-21促进HL-7702细胞葡萄糖的消耗且呈剂量依赖性,与胰岛素联合用药提高葡萄糖消耗量。在随后IR模型实验中,FGF-21改善IR模型细胞葡萄糖消耗量。FGF-21作用24 h,GLUT1的表达量明显增高,p-ERK1/2的含量增强。当加入ERK1/2特异性抑制剂PD98059,FGF-21促ERK1/2的磷酸化作用被抑制。IR模型中,FGF-21仍能提高p-ERK1/2的含量。结论 FGF-21促进HL-7702细胞对葡萄糖的消耗,改善IR HL-7702细胞葡萄糖消耗量,提高葡萄糖转运蛋白GLUT1和ERK1/2磷酸化的表达。     

依那普利对2型糖尿病大鼠血浆AngII水平及血管、肾脏AT_1受体表达的影响

目的　研究依那普利对2型糖尿病大鼠血浆AngII和AT1受体表达的影响。方法用放射免疫法测定 血浆AngII水平,免疫组化法观察血管和肾脏AT1受体表达。结果　糖尿病大鼠血浆AngII明显高于对照组,应用依那普利后大鼠血浆AngII明显降低。免疫组化染色发现糖尿病大鼠血管内皮细胞、平滑肌细胞和肾脏AT1受体表达明显增加,依那普利治疗组大鼠血管内皮细胞、平滑肌细胞和肾脏AT1受体表达与正常组接近。结论　糖尿病大 鼠血浆AngII升高,血管和肾脏AT1受体表达增加,依那普利可降低糖尿病大鼠血浆AngII水平,下调血管和肾脏 AT受体表达。     

心力衰竭时大鼠下丘脑室旁核内血管紧张素1型受体的变化对交感神经活动的影响

目的观察心力衰竭时大鼠下丘脑室旁核内血管紧张素1型受体(AT1-R)可能发生的改变及其对交感神经活动的影响。方法选取雄性SD大鼠,首先进行室旁核插管术,1周后采用左侧冠状动脉结扎术建立大鼠心力衰竭模型或假手术模型,同时各组大鼠分别经微型渗透泵通过室旁核插管持续给予AT1-R阻滞剂缬沙坦(VAL)0.05μg/h或人工脑脊液(aCSF)0.11μl/h干预。4周后检测心功能;电生理记录肾交感神经放电;计算肺/体质量比(L/BW)和右心室/体质量比(RVW/BW);测定血浆去甲肾上腺素(NE)和血管紧张素Ⅱ(AngⅡ)含量;Western blot技术检测下丘脑室旁核内Fra-like和AT1-R蛋白表达情况。结果与假手术组比较,冠状动脉结扎术后4周大鼠的心功能明显降低;血浆NE和AngⅡ浓度增高(P<0.05);肾交感神经放电明显增强;室旁核内Fra-like和AT1-R蛋白表达增加(P<0.05)。与人工脑脊液治疗组比较,接受缬沙坦治疗的心力衰竭大鼠心功能有所改善,外周血NE和AngⅡ含量下降(P<0.05),肾交感神经放电减少(P<0.05),室旁核区域的Fra-like和AT1-R表达明显减少(P<0.05)。结论心力衰竭时室旁核区域的AT1-R被明显激活伴有交感神经放电增加,促进心力衰竭的发展。     

Characterization of angiotensin II antagonism displayed by Ib, a novel nonpeptide angiotensin AT(1) receptor antagonist

The pharmacologic profile of Ib, 5-n-butyl-4-{4-[2-(1H-tetrazole-5-yl)-1H-pyrrol-1-yl]phenylmethyl}-2,4-dihydro-2-(2,6-dichloridephenyl)-3H-1,2,4-triazol-3-one, a novel nonpeptide angiotensin AT(1) receptor antagonist, was investigated by receptor-binding studies, functional in vitro assays with rabbit and rat aorta, and in vivo experiments in rats. Ib inhibited [(125)I] angiotensin II binding to AT(1) receptors in rat liver membranes (K(i)=2.5+/-0.5 nM) and did not interact with AT(2) receptors in bovine cerebellar membranes. In functional studies with rat and rabbit aorta, Ib inhibited the contractile response to angiotensin II (pD(2)' value: 7.43 and 7.29, respectively) with a significant reduction in the maximum. In pithed rats, Ib inhibited the angiotensin II induced pressor response in a dose-related manner. After intravenous administration, Ib produced a dose-dependent antihypertensive effects in spontaneously hypertensive rats and renal hypertensive rats. These results suggest that Ib is a potent angiotensin AT(1) selective receptor antagonist with a mode of insurmountable antagonism.     

血管紧张素-(1-7)对血管紧张素II致人脐静脉内皮细胞损伤的保护作用研究

目的 :观察血管紧张素 (1 7) [Ang (1 7) ]对血管紧张素II(AngII)致人脐静脉内皮细胞 (HU VECs)损伤的保护作用。方法 :体外培养的HUVECs随机分为 4组 :对照组 ,AngII组 ,Ang (1 7)组 ,AngII Ang (1 7)组。采用分光光度计测定培养的HU VECs乳酸脱氢酶 (LDH)漏出 ;流式细胞仪检测细胞凋亡 ;硝酸还原酶法和放射免疫分析技术分别测定HUVECs上清液中一氧化氮 (NO)和内皮素 1(ET 1)的含量。结果 :与对照组比较 ,AngII(0 .1μmol·L-1)显著增加HUVECsLDH漏出 (P <0 .0 1)、ET 1分泌(P <0 .0 1)和HUVECs凋亡率 (P <0 .0 1) ,显著减少NO的含量 (P <0 .0 5 ) ;Ang (1 7)呈剂量依赖性抑制了AngII的促LDH漏出、ET 1分泌、增加细胞凋亡等作用 ,同时明显促进HUVECs的NO释放 ;单用Ang (1 7)对HUVECs无明显影响。结论 :Ang (1 7)可抑制AngII所致的体外培养HUVECs损伤 ,对内皮细胞具有保护作用。     

Angiotensin-induced EGF receptor transactivation inhibits insulin signaling in C9 hepatic cells

To investigate the potential interactions between the angiotensin II (Ang II) and insulin signaling systems, regulation of IRS-1 phosphorylation and insulin-induced Akt activation by Ang II were examined in clone 9 (C9) hepatocytes. In these cells, Ang II specifically inhibited activation of insulin-induced Akt Thr³⁰⁸ and its immediate downstream substrate GSK-3α/β in a time-dependent fashion, with ∼70% reduction at 15 min. These inhibitory actions were associated with increased IRS-1 phosphorylation of Ser⁶³⁶/Ser⁶³⁹ that was prevented by selective blockade of EGFR tyrosine kinase activity with AG1478. Previous studies have shown that insulin-induced phosphorylation of IRS-1 on Ser⁶³⁶/Ser⁶³⁹ is mediated mainly by the PI3K/mTOR/S6K-1 sequence. Studies with specific inhibitors of PI3K (wortmannin) and mTOR (rapamycin) revealed that Ang II stimulates IRS-1 phosphorylation of Ser⁶³⁶/Ser⁶³⁹ via the PI3K/mTOR/S6K-1 pathway. Both inhibitors blocked the effect of Ang II on insulin-induced activation of Akt. Studies using the specific MEK inhibitor, PD98059, revealed that ERK1/2 activation also mediates Ang II-induced S6K-1 and IRS-1 phosphorylation, and the impairment of Akt Thr³⁰⁸ and GSK-3α/β phosphorylation. Further studies with selective inhibitors showed that PI3K activation was upstream of ERK, suggesting a new mechanism for Ang II-induced impairment of insulin signaling. These findings indicate that Ang II has a significant role in the development of insulin resistance by a mechanism that involves EGFR transactivation and the PI3K/ERK1/2/mTOR-S6K-1 pathway.     

The effects of KT3-671, a new angiotensin II (AT 1) receptor blocker in mild to moderate hypertension

AIMS: To compare the antihypertensive effect, and tolerability and safety of once daily doses of KT3-671 with that of placebo in patients with mild to moderate uncomplicated essential hypertension. METHODS: A randomised, multicentre, double blind, parallel-group comparison of KT3-671 with placebo. Hypertensive patients [Ambulatory Blood Pressure Monitoring (ABPM), mean daytime DBP > 90 mmHg, Office sitting mean DBP 95-114 after a 7-28 day washout period] entered a 2-week, single blind, run-in phase. Patients eligible for the double-blind phase were randomised to receive KT3-671 40 mg, 80 mg, 160 mg or placebo once daily over 4 weeks. The primary end-point was trough mean sitting office DBP. The study had 90% power to detect a 5 mmHg change between treatments and placebo at the 5% level of significance. The secondary end-points were 24 hour, daytime and night time mean ABPM. RESULTS: Office DBP was significantly lower with KT3-671 40 mg but not the other 2 dosage groups (-3.2; 95% CL -6.1 : -0.3 P < 0.03). Office SBP was significantly reduced with all dosage groups (40 mg -5.9, 95% CL -11 : -0.9; 80 mg -4.9, 95% CL -9.9 : 0.1 and 160 mg -5.7, 95% CL -10.8 : -0.7 P < 0.05). All doses of KT3-671 reduced systolic and diastolic ABPM. The number of patients with treatment related adverse events were comparable to placebo (38.8% KT3-671 vs 32.8% placebo). There was some evidence of a dose-response relationship with fall in nocturnal ABPM. CONCLUSIONS: Oral KT3-671 was well tolerated. KT3-671 reduced office systolic BP at all doses and diastolic BP at some of the doses. Due to greater precision and power, the falls in mean ambulatory systolic and diastolic pressure were all significantly lower than placebo.     

Arsenic upregulates the expression of angiotensin II Type I receptor in mouse aortic endothelial cells

Although chronic arsenic exposure is a well-known risk for cardiovascular disease and has a strong correlation with hypertension, the molecular pathogenesis underlying arsenic exposure-induced hypertension remains poorly understood. To delineate the pathogenesis, we examined changes in the mRNA levels of 2 angiotensin II Type I receptor (AT₁R) subtypes, AT_1AR and AT_1BR, in a mouse aortic endothelial cell line, END-D. Quantitative real-time PCR analysis revealed significant increases in the mRNA levels of 2 AT₁R subtypes, AT_1AR and AT_1BR following sodium arsenite (SA) treatment. Flow cytometry analysis revealed that SA increases the generation of reactive oxygen species (ROS) in a dose-dependent manner. In addition, western blot analysis revealed that SA enhances the phosphorylations of c-Jun N-terminal kinases (JNK) and activated protein 1 (AP-1). These phosphorylations were inhibited by N-acetylcysteine (NAC), an anti-oxidant. Finally, SA-induced AT₁R expression was found to be prevented both by NAC and specific JNK inhibitor, SP6001325, strongly indicating that AT₁R upregulation is a result of the ROS-mediated activation of the JNK signaling pathway. Taken together, our results indicate that arsenic indeed upregulates the AT₁R expression, thus highlighting a role of arsenic-induced aberrant AT₁R signaling in the pathogenesis of hypertension.     

AT1 receptor blocker-insensitive mutant AT1A angiotensin receptors reveal the presence of G protein-independent signaling in C9 cells

Although mutant receptors are highly useful to dissect the signal transduction pathways of receptors, they are difficult to study in physiological target tissues, due to the presence of endogenous receptors. To study AT(1) angiotensin receptors in their physiological environment, we constructed a mutant receptor, which differs only from the AT(1A) receptor in its reduced affinity for candesartan, a biphenylimidazole antagonist. We have determined that the conserved S109Y substitution of the rat AT(1A) receptor eliminates its candesartan binding, without exerting any major effect on its angiotensin II and peptide angiotensin receptor antagonist binding, internalization kinetics, beta-arrestin binding, and potency or efficacy of the inositol phosphate response. To demonstrate the usefulness of this mutant receptor in signal transduction studies, we combined it with substitution of the highly conserved DRY sequence with AAY, which abolishes G protein activation. In rat C9 hepatocytes the S109Y receptor caused ERK activation with the same mechanism as the endogenous AT(1) receptor. After combination with the DRY/AAY mutation G protein-independent ERK activation was detected demonstrating that this approach can be used to study the angiotensin II-stimulated signaling pathways in cells endogenously expressing AT(1) receptors.     

Angiotensin II type 1 receptor <Emphasis Type="Italic">1166A/C</Emphasis> polymorphism in association with blood pressure response to exogenous angiotensin II

Background The angiotensin II type 1 receptor (AT1R) 1166A/C polymorphism is reported to be implicated in cardiovascular diseases. The association between the 1166A/C polymorphism and diastolic blood pressure (DBP) changes in response to exogenous angiotensin II and valsartan was evaluated by pharmacokinetic and pharmacodynamic modeling. Methods Thirteen normotensive, healthy adults (six with the 1166A/A polymorphism and seven with 1166A/C) were enrolled in this clinical study. Angiotensin II was infused continuously over a 2-min period at four different rates (from 5 ng/kg/min and increased by 5 ng/kg/min) at 0 (before valsartan dosing), 2, 4, 8, 12, and 24 h after a single oral dose of valsartan (40 mg). BP was measured serially before and at the end of each rate of angiotensin II infusion. Plasma concentration-time profiles of valsartan were established over a 24-h period. We analyzed data using NONMEM and studied the relationship between the AT1R 1166A/C genotypes and BP responses. Results Plasma valsartan concentrations and DBP data best fitted into a two-compartment linear model and E_max model (E_max with baseline for angiotensin II and inhibitory E_max for valsartan), respectively. The ED50 for angiotensin II in the subjects with 1166A/C [95% confidence interval (CI): 4.30∼14.02 ng/kg/min] was significantly lower than in those with 1166A/A (95% CI: 14.23∼28.77 ng/kg/min), while the E_max for angiotensin II and EC50 for valsartan was similar in both genotype groups. Conclusions These results suggest that exogenous human angiotensin II increases the BP more potently in subjects with 1166A/C than in those with 1166A/A.     

Comparison of glycemic variability in Japanese patients with type 1 diabetes receiving insulin degludec versus insulin detemir using continuous glucose monitoring: a randomized,cross-over,pilot study

Objective: To use continuous glucose monitoring (CGM) to compare glycemic variability in patients with type 1 diabetes (T1D) treated with insulin degludec (IDeg) versus insulin detemir (IDet).

Methods: Ten patients with T1D were randomly assigned to receive once-daily IDeg, followed by twice-daily IDet, or vice versa. Glucose variability was evaluated by CGM after >4 weeks of the first insulin and again after crossover to the second insulin.

Results: The total daily insulin dose (U/kg/day) and the total daily basal insulin dose (U/kg/day) were significantly lower during treatment with IDeg than with IDet [median (interquartile range): 0.55 (0.54–0.73) vs. 0.64 (0.54–0.83); P = 0.028, 0.24 (0.19–0.36) vs. 0.30 (0.19–0.39); P = 0.027]. The 24-hour mean glucose levels were not significantly different. However, their standard deviation (SD) was significantly smaller during treatments with IDeg than those with IDet [59.5 (39.5–71.0) vs. 72.8 (61.8–92.8); P = 0.008]. Their mean fasting glucose levels and the mean postprandial peak levels after breakfast and after dinner were significantly lower with IDeg.

Conclusions: A CGM-based comparison demonstrated that once-daily IDeg showed fewer glycemic fluctuations than twice-daily IDet. IDeg appears to stabilize blood glucose levels better during both daytime and nighttime (particularly, before and after breakfast) with a lower insulin dosage.     

依那普利对2型糖尿病大鼠血浆Ang II水平及血管、肾脏AT1受体表达的影响

目的研究依那普利对2型糖尿病大鼠血浆Ang II和AT₁受体表达的影响。方法用放射免疫法测定血浆Ang II水平，免疫组化法观察血管和肾脏AT₁受体表达。结果糖尿病大鼠血浆Ang II明显高于对照组，应用依那普利后大鼠血浆Ang II明显降低。免疫组化染色发现糖尿病大鼠血管内皮细胞、平滑肌细胞和肾脏AT₁受体表达明显增加，依那普利治疗组大鼠血管内皮细胞、平滑肌细胞和肾脏AT₁受体表达与正常组接近。结论糖尿病大鼠血浆Ang II升高，血管和肾脏AT₁受体表达增加，依那普利可降低糖尿病大鼠血浆Ang II水平，下调血管和肾脏AT₁受体表达。