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 (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.