| Abstrakt: |
The acute effects of angiotensin-1–7 [ANG-(1–7)] on the reabsorptive bicarbonate flow (JHCO3−) 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 JHCO3−was 2.40 ± 0.10 nmol·cm−2·s−1(n= 120); losartan (10−7M) or A779 (10−6M, a specific Mas antagonist), alone or in combination with losartan, decreased the JHCO3−. ANG-(1–7) had biphasic effects on JHCO3−: at 10−9M, it inhibited, and at 10−6, it stimulated the flow. S3226 [10−6M, a specific Na+-H+exchanger 3 (NHE3) antagonist] decreased JHCO3−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 10−9M increased JHCO3−, and ANG-(1–7) at 10−6M reduced it. The effects of A779, losartan, and S3226 on the JHCO3−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 ~100 nM and was increased by ANG-(1–7) at 10−9or 10−6M. 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. |
