The effects of angiotensin-(1–7) on the exchanger NHE3 and on [Ca2+]i in the proximal tubules of spontaneously hypertensive rats

Abstract

The acute effects of angiotensin-1–7 [ANG-(1–7)] on the reabsorptive bicarbonate flow (J[Formula: see text]) 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 J[Formula: see text] 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 J[Formula: see text]. ANG-(1–7) had biphasic effects on J[Formula: see text]: 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 J[Formula: see text] 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 J[Formula: see text] 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 J[Formula: see text], and ANG-(1–7) at 10−6 M reduced it. The effects of A779, losartan, and S3226 on the J[Formula: see text] 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 10−9 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.