The effects of angiotensin-(1-7) on the exchanger NHE3 and on [Ca2+] i in the proximal tubules of spontaneously hypertensive rats
The effects of angiotensin-(1-7) on the exchanger NHE3 and on [Ca2+] i in the proximal tubules of spontaneously hypertensive rats
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DOI：
10.1152/ajprenal.00557.2016
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发表时间：
2017-08-01
影响因子：
4.2
通讯作者：
de Mello-Aires, Margarida
中科院分区：
文献类型：
--
作者：
Castelo-Branco, Regiane Cardoso;Leite-Dellova, Deise C. A.;de Mello-Aires, Margarida
在自发性高血压大鼠（SHR）和正常血压对照大鼠（WKY）的近端小管中，使用对H+敏感的微电极，通过体内静态微灌注，评价了血管紧张素1-7 [ANG-（1-7）]对重吸收碳酸氢盐流（JHCO（3）（-））的急性作用。在WKY大鼠中，对照组JHCO（3）（-）为2.40 +/- 0.10 nmol.cm（-2）.s（-1）（n = 120）;氯沙坦（10（-7）M）或A779（10（-6）M，一种特异性Mas拮抗剂）单独或与氯沙坦联合使用可降低JHCO（3）（-）。ANG-（1-7）对JHCO（3）（-）有双相作用：在10（-9）M时，它抑制血流，在10（-6）M时，它刺激血流。S3226 [10（-6）M，一种特异性Na+-H+交换器3（NHE 3）拮抗剂]使JHCO（3）（-）降低，使ANG-（1-7）的刺激作用变为抑制作用，但不改变ANG-（1-7）的抑制作用。在SHR中，对照JHCO 3-为2.04 +/- 0.13 nmol.cm（-2）.s（-1）（n = 56），并且A779和/或氯沙坦减少了流量。10-9 M的ANG-（1-7）增加JHCO（3）（-），10-6 M的ANG-（1-7）减少JHCO（3）（-）。A779、氯沙坦和S3226对JHCO（3）（-）的作用与WKY大鼠相似，这表明在SHR中，ANG-（1-7）对NHE 3的作用是通过Mas和ANG II 1型。WKY或SHR大鼠的胞浆钙浓度与100 nM相似，10（-9）或10（-6）M的ANG-（1-7）可使其升高。在高血压动物中，高血浆ANG-（1-7）水平抑制近端小管中的NHE 3，从而减轻由高血浆ANG II水平引起的高血压。
The acute effects of angiotensin-1-7 [ANG-(1-7)] on the reabsorptive bicarbonate flow (JHCO(3)(-)) were evaluated using stationary microperfusion in vivo in the proximal tubules of spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar-Kyoto (WKY) rats, using a microelectrode sensitive to H+. In WKY rats, the control JHCO(3)(-) was 2.40 +/- 0.10 nmol.cm(-2).s(-1) (n = 120); losartan (10(-7) M) or A779 (10(-6) M, a specific Mas antagonist), alone or in combination with losartan, decreased the JHCO(3)(-). ANG-(1-7) had biphasic effects on JHCO(3)(-) : at 10(-9) M, it inhibited, and at 10(-6), it stimulated the flow. S3226 [10(-6) M, a specific Na+-H+ exchanger 3 (NHE3) antagonist] decreased JHCO(3)(-) and changed the stimulatory effect of ANG-(1-7) to an inhibitory one but did not alter the inhibitory action of ANG-(1-7). In SHR, the control JHCO3- was 2.04 +/- 0.13 nmol.cm(-2).s(-1)(n = 56), and A779 and/or losartan reduced the flow. ANG-(1-7) at 10-9 M increased JHCO(3)(-), and ANG-(1-7) at 10-6 M reduced it. The effects of A779, losartan, and S3226 on the JHCO(3)(-) were similar to those found in WKY rats, which indicated that in SHR, the ANG-(1-7) action on the NHE3 was via Mas and ANG II type 1. The cytosolic calcium in the WKY or SHR rats was similar to 100 nM and was increased by ANG-(1-7) at 10(-9) or 10(-6) M. In hypertensive animals, a high plasma level of ANG-(1-7) inhibited NHE3 in the proximal tubule, which mitigated the hypertension caused by the high plasma level of ANG II.