Renal actions of angiotensin-(1-7): In vivo and in vitro studies
Renal actions of angiotensin-(1-7): In vivo and in vitro studies
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DOI：
10.1152/ajprenal.1996.270.1.f141
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发表时间：
1996-01-01
影响因子：
4.2
通讯作者：
Strandhoy, JW
中科院分区：
文献类型：
--
作者：
Handa, RK;Ferrario, CM;Strandhoy, JW
体内研究在去神经支配肾脏的充满Na的麻醉雄性Wistar大鼠中进行。肾内注射>1 nmol/kg的血管紧张素-（1 - 7）[ANG-（1-7）]可引起肾血流量的轻度剂量依赖性减少，这是由AT（1）型ANG II受体介导的。肾内持续输注ANG-（1-7）0.1和1 nmol . min（-1）。kg（-1）对肾血流量和血压的影响最小，与时间控制盐水输注组相比，导致钠和水的尿排泄量增加。为了确定ANG-（1-7）是否可能对肾小管上皮细胞具有直接作用以抑制钠重吸收，我们在体外检查了ANG（1-7）对大鼠近端小管新鲜悬浮液中转运依赖性O-2消耗（QO（2））的影响。ANG-（1-7）以浓度依赖性方式抑制QO（2），其阈值浓度类似于100 pM。用制霉菌素刺激Na-K-腺苷三磷酸酶（Na-K-ATPase）活性，使ANG-（1-7）的抑制浓度-反应曲线显著移动。用5 mM哇巴因预处理可消除1 pMANG-（1-7）对QO（2）22%的抑制作用（Na-K-ATP酶抑制剂），用1 μ M PD-123319（AT（2）受体拮抗剂）预处理未改变，用1 μ M氯沙坦（AT（1）受体拮抗剂）部分减弱，用1 μ M消除[Sar（1），Thr（8）]ANG II（非选择性ANG受体拮抗剂）。总之，这些发现表明ANG-（1-7）在肾脏中具有生物活性，并且在非血管收缩剂剂量下，导致体内Na和水排泄增加。一个作用位点是近端小管，在那里ANG-（1-7）可以抑制细胞Na转运中的哇巴因敏感性Na-K-ATP酶退出步骤。ANG-（1-7）的这种新的抑制作用似乎是由AT（1）受体（次要组分）和非AT（1）、非AT（2）ANG受体（主要组分）介导的。
In vivo studies were conducted in Na-replete anesthetized male Wistar rats with denervated kidneys. Intrarenal injections of angiotensin-(1-7) [ANG-(1-7)] at >1 nmol/kg produced a shallow dose-dependent decrease in renal blood flow that was mediated by the AT(1)-type ANG II receptor. A constant intrarenal infusion of ANG-(1-7) at 0.1 and 1 nmol . min(-1). kg(-1) had minimal effects on renal blood flow and blood pressure and resulted in an elevated urinary excretion of Na and water compared with the time-control saline-infused group. To determine whether ANG-(1-7) may have a direct action on tubular epithelium to inhibit Na reabsorption, we examined the effect of ANG(1-7) on transport-dependent O-2 consumption (QO(2)) in fresh suspensions of rat proximal tubules in vitro. ANG-(1-7) inhibited QO(2) in a concentration-dependent fashion with a threshold concentration of similar to 100 pM. Stimulating Na-K-adenosinetriphosphatase (Na-K-ATPase) activity with nystatin caused a leftward shift of the inhibitory concentration-response curve to ANG-(1-7). The 22% inhibition of QO(2) by 1 pM ANG-(1-7) was abolished by pretreatment with 5 mM ouabain (Na-K-ATPase inhibitor), unaltered by pretreatment with 1 mu M PD-123319 (AT(2) receptor antagonist), partially attenuated by 1 mu M losartan (AT(1) receptor antagonist), and abolished by 1 mu M [Sar(1),Thr(8)]ANG II (nonselective ANG receptor antagonist). Together these findings indicate that ANG-(1-7) has biological activity in the kidney and, at nonvasoconstrictor doses, results in increased Na and water excretion in vivo. One site of action is the proximal tubule, where ANG-(1-7) can inhibit an ouabain-sensitive Na-K-ATPase exit step in cellular Na transport. This novel inhibitory action of ANG-(1-7) appears to be mediated by an AT(1) receptor (minor component) and a non-AT(1), non-AT(2) ANG receptor (major component).