Castro-Moreno P, Pardo J P, Hernández-Muñoz R, López-Guerrero J J, Del Valle-Mondragón L, Pastelín-Hernández G, Ibarra-Barajas M, Villalobos-Molina R
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico.
Auton Autacoid Pharmacol. 2012 Oct;32(3 Pt 4):61-9. doi: 10.1111/aap.12001.
We investigated captopril effects, an ACE inhibitor, on hypertension development, on Ang II and Ang-(1-7) plasma concentrations, on Ang II-induced contraction in isolated kidneys, and on kidney AT1R from spontaneously hypertensive (SHR) rats. Five weeks-old SHR and Wistar Kyoto (WKY) rats were treated with captopril at 30 mg/kg/day, in drinking water for 2 or 14 weeks. Systolic blood pressure (SBP) was measured, and isolated kidneys were tested for perfusion pressure and AT1R expression; while Ang II and Ang-(1-7) concentrations were determined in plasma. Captopril did not modify SBP in WKY rats and avoided its increase as SHR aged. Plasma Ang-II concentration was ∼4-5 folds higher in SHR rats, and captopril reduced it (P<0.05); while captopril increased Ang-(1-7) by ∼2 fold in all rat groups. Captopril increased Ang II-induced pressor response in kidneys of WKY and SHR rats, phenomenon not observed in kidneys stimulated with phenylephrine, a α₁-adrenoceptor agonist. Captopril did not modify AT1R in kidney cortex and medulla among rat strains and ages. Data indicate that captopril increased Ang II-induced kidney perfusion pressure but not AT₁R density in kidney of WKY and SHR rats, due to blockade of angiotensin II synthesis; however, ACE inhibitors may have other actions like activating signaling processes that could contribute to their diverse effects.
我们研究了血管紧张素转换酶（ACE）抑制剂卡托普利对自发性高血压（SHR）大鼠高血压发展、血浆血管紧张素II（Ang II）和血管紧张素-(1-7)（Ang-(1-7)）浓度、Ang II诱导的离体肾脏收缩以及肾脏血管紧张素II 1型受体（AT1R）的影响。5周龄的SHR大鼠和Wistar Kyoto（WKY）大鼠以30 mg/kg/天的剂量在饮用水中给予卡托普利，持续2周或14周。测量收缩压（SBP），并对离体肾脏进行灌注压力和AT1R表达测试；同时测定血浆中Ang II和Ang-(1-7)的浓度。卡托普利对WKY大鼠的SBP没有影响，并避免了SHR大鼠随着年龄增长SBP的升高。SHR大鼠的血浆Ang-II浓度比WKY大鼠高约4-5倍，卡托普利使其降低（P<0.05）；而卡托普利在所有大鼠组中使Ang-(1-7)增加了约2倍。卡托普利增加了WKY和SHR大鼠肾脏中Ang II诱导的升压反应，而在用α₁-肾上腺素能受体激动剂去氧肾上腺素刺激的肾脏中未观察到这种现象。卡托普利在不同品系和年龄的大鼠肾脏皮质和髓质中对AT1R没有影响。数据表明，由于血管紧张素II合成受阻，卡托普利增加了WKY和SHR大鼠肾脏中Ang II诱导的灌注压力，但没有改变肾脏中AT₁R的密度；然而，ACE抑制剂可能还有其他作用，如激活信号转导过程，这可能导致它们产生多种效应。
