Cao Gabriel, Della Penna Silvana Lorena, Kouyoumdzian Nicolás Martín, Choi Marcelo Roberto, Gorzalczany Susana, Fernández Belisario Enrique, Toblli Jorge Eduardo, Rosón María Inés
Gabriel Cao, Silvana Lorena Della Penna, Nicolás Martín Kouyoumdzian, Marcelo Roberto Choi, Belisario Enrique Fernández, Jorge Eduardo Toblli, María Inés Rosón, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires C1122AAJ, Argentina.
World J Nephrol. 2017 Jan 6;6(1):29-40. doi: 10.5527/wjn.v6.i1.29.
To determine the effect of tempol in normal rats fed high salt on arterial pressure and the balance between antagonist components of the renal renin-angiotensin system.
Sprague-Dawley rats were fed with 8% NaCl high-salt (HS) or 0.4% NaCl (normal-salt, NS) diet for 3 wk, with or without tempol (T) (1 mmol/L, administered in drinking water). Mean arterial pressure (MAP), glomerular filtration rate (GFR), and urinary sodium excretion (UVNa) were measured. We evaluated angiotensin II (Ang II), angiotensin 1-7 (Ang 1-7), angiotensin converting enzyme 2 (ACE2), mas receptor (MasR), angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R) in renal tissues by immunohistochemistry.
The intake of high sodium produced a slight but significant increase in MAP and differentially regulated components of the renal renin-angiotensin system (RAS). This included an increase in Ang II and AT1R, and decrease in ACE-2 staining intensity using immunohistochemistry. Antioxidant supplementation with tempol increased natriuresis and GFR, prevented changes in blood pressure and reversed the imbalance of renal RAS components. This includes a decrease in Ang II and AT1R, as increase in AT2, ACE2, Ang (1-7) and MasR staining intensity using immunohistochemistry. In addition, the natriuretic effects of tempol were observed in NS-T group, which showed an increased staining intensity of AT2, ACE2, Ang (1-7) and MasR.
These findings suggest that a high salt diet leads to changes in the homeostasis and balance between opposing components of the renal RAS in hypertension to favour an increase in Ang II. Chronic antioxidant supplementation can modulate the balance between the natriuretic and antinatriuretic components of the renal RAS.
确定Tempol对高盐喂养的正常大鼠动脉血压及肾素-血管紧张素系统拮抗成分平衡的影响。
将Sprague-Dawley大鼠分为4组,分别给予8% NaCl高盐(HS)或0.4% NaCl(正常盐,NS)饮食3周,其中两组分别添加或不添加Tempol(T)(1 mmol/L,通过饮用水给予)。测量平均动脉压(MAP)、肾小球滤过率(GFR)和尿钠排泄量(UVNa)。采用免疫组织化学法评估肾组织中血管紧张素II(Ang II)、血管紧张素1-7(Ang 1-7)、血管紧张素转换酶2(ACE2)、mas受体(MasR)、血管紧张素1型受体(AT1R)和血管紧张素2型受体(AT2R)。
高钠摄入使MAP略有但显著升高,并对肾素-血管紧张素系统(RAS)的成分进行了不同调节。这包括免疫组织化学显示Ang II和AT1R增加,ACE-2染色强度降低。补充抗氧化剂Tempol可增加尿钠排泄和GFR,预防血压变化,并逆转肾RAS成分的失衡。这包括免疫组织化学显示Ang II和AT1R减少,AT2、ACE2、Ang(1-7)和MasR染色强度增加。此外,在NS-T组中观察到Tempol的利钠作用,其AT2、ACE2、Ang(1-7)和MasR染色强度增加。
这些发现表明,高盐饮食会导致高血压中肾RAS相反成分之间的稳态和平衡发生变化,有利于Ang II增加。长期补充抗氧化剂可调节肾RAS利钠和抗利钠成分之间的平衡。