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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.

Chronic angiotensin II (ANG II) infusion for 1 or 2 wk leads to progressive hypertension and induces inward hypertrophic remodeling in preglomerular vessels, which is associated with increased renal vascular resistance (RVR) and decreased glomerular perfusion. Considering the ability of preglomerular vessels to exhibit adaptive responses, the present study was performed to evaluate glomerular perfusion and renal function after 6 wk of ANG II infusion. To address this study, male Wistar rats were submitted to sham surgery (control) or osmotic minipump insertion (ANG II 200 ng·kg−1·min−1, 42 days). A group of animals was treated or cotreated with losartan (10 mg·kg−1·day−1), an AT1receptor antagonist, between days 28and 42. Chronic ANG II infusion increased systolic blood pressure to 185 ± 4 compared with 108 ± 2 mmHg in control rats. Concomitantly, ANG II-induced hypertension increased intrarenal ANG II level and consequently, preglomerular and glomerular injury. Under this condition, ANG II enhanced the total renal plasma flow (RPF), glomerular filtration rate (GFR), urine flow and induced pressure natriuresis. These changes were accompanied by lower RVR and enlargement of the lumen of interlobular arteries and afferent arterioles, consistent with impairment of renal autoregulatory capability and outward preglomerular remodeling. The glomerular injury culminated with podocyte effacement, albuminuria, tubulointerstitial macrophage infiltration and intrarenal extracellular matrix accumulation. Losartan attenuated most of the effects of ANG II. Our findings provide new information regarding the contribution of ANG II infusion over 2 wk to renal hemodynamics and function via the AT1receptor.