Shibasaki Y, Mori Y, Tsutumi Y, Masaki H, Sakamoto K, Murasawa S, Maruyama K, Moriguchi Y, Tanaka Y, Iwasaka T, Inada M, Matsubara H
Department of Medicine II, Kansai Medical University, Moriguchi, Osaka, Japan.
Clin Nephrol. 1999 Feb;51(2):83-91.
Angiotensin II (Ang II) C-terminal hexapeptide (referred to as Ang IV) possesses the characteristics of a real hormone with specific receptors and biological effects. Clinical application of Ang II type 1 receptor (AT1-R) antagonists cause an increase in plasma Ang II level, which may result in enhanced production of Ang IV.
In this study, we measured plasma Ang IV and Ang II levels in patients with chronic renal failure (CRF), and also examined the changes in Ang IV and Ang II levels after administration of an ATI-R antagonist.
Ang II and Ang IV levels in CRF patients untreated with hemodialysis (n = 16) were 15.8+/-3.6 and 6.0+/-1.1 pg/ml, respectively, which did not differ significantly from Ang II (20.6+/-2.4) and Ang IV levels (8.6+/-1.1) in normal controls (n = 23). The ratio of Ang IV to Ang II was 38%, similar to that in the controls (41%). Ang II or Ang IV levels in CRF patients treated with hemodialysis (n = 12) were also similar to the control values. Ang IV levels had a significant correlation with Ang II levels (r = 0.59). When hypertensive patients were treated with an AT1-R antagonist candesartan for 7 days, Ang II and Ang IV levels were increased 5.5- and 4.1-fold relative to the control levels, respectively. Ang II levels 28 and 56 days after treatment were significantly lower than those 7 days after treatment, whereas Ang IV levels did not differ significantly from those 7 days after treatment. Similar differential kinetics in Ang II and Ang IV levels after long-term (90 days) treatment with an AT1-R antagonist was also confirmed in experiments using rats. Significant decrease in blood pressure continued during long-term treatment with an AT1-R antagonist.
These findings demonstrated that plasma Ang IV levels in patients with CRF did not differ significantly from those in normal subjects, and that treatment with an AT1-R antagonist caused marked increases in both Ang II and Ang IV levels. In contrast, during long-term treatment plasma Ang II levels were more rapidly decreased than Ang IV levels, suggesting longer-lasting enhancement of the action of Ang IV rather than that of Ang II after treatment with an AT1-R antagonist.
血管紧张素II（Ang II）的C末端六肽（称为Ang IV）具有真正激素的特征，具有特定受体和生物学效应。1型血管紧张素II受体（AT1-R）拮抗剂的临床应用会导致血浆Ang II水平升高，这可能会导致Ang IV生成增加。
在本研究中，我们测量了慢性肾衰竭（CRF）患者的血浆Ang IV和Ang II水平，并观察了给予AT1-R拮抗剂后Ang IV和Ang II水平的变化。
未接受血液透析治疗的CRF患者（n = 16）的Ang II和Ang IV水平分别为15.8±3.6和6.0±1.1 pg/ml，与正常对照组（n = 23）的Ang II（20.6±2.4）和Ang IV水平（8.6±1.1）相比，差异无统计学意义。Ang IV与Ang II的比值为38%，与对照组（41%）相似。接受血液透析治疗的CRF患者（n = 12）的Ang II或Ang IV水平也与对照值相似。Ang IV水平与Ang II水平显著相关（r = 0.59）。高血压患者用AT1-R拮抗剂坎地沙坦治疗7天后，Ang II和Ang IV水平分别相对于对照水平升高了5.5倍和4.1倍。治疗后28天和56天的Ang II水平显著低于治疗后7天，而Ang IV水平与治疗后7天相比差异无统计学意义。在大鼠实验中也证实了长期（90天）使用AT1-R拮抗剂治疗后Ang II和Ang IV水平的类似差异动力学。长期使用AT1-R拮抗剂治疗期间血压持续显著下降。
这些发现表明，CRF患者的血浆Ang IV水平与正常受试者相比无显著差异，并且用AT1-R拮抗剂治疗会导致Ang II和Ang IV水平显著升高。相反，在长期治疗期间，血浆Ang II水平比Ang IV水平下降得更快，这表明在使用AT1-R拮抗剂治疗后，Ang IV的作用增强持续时间比Ang II更长。
