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Dose‐dependent effects of Angiotensin‐(1–7) and Angiontensin II on the NHE3 exchanger in in vivo proximal tubule of spontaneously hypertensive rats
Author(s) -
Branco Regiane Cardoso Castelo,
LeiteDellova Deise Carla Almeida,
Malnic Gerhard,
MelloAires Margarids
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.967.22
Subject(s) - losartan , chemistry , endocrinology , angiotensin ii , medicine , sodium–hydrogen antiporter , reabsorption , renin–angiotensin system , antagonist , angiotensin ii receptor type 1 , in vivo , receptor , kidney , blood pressure , sodium , biology , microbiology and biotechnology , organic chemistry
The action of Angiotensin‐(1‐7) [Ang‐(1‐7) on the NHE3 exchanger contributes to the understanding of the etiology of hypertension in spontaneously hypertensive rats (SHR) and their controls, Wistar‐Kyoto rats (WKY). This action was evaluated by bicarbonate reabsorption (JHCO 3 − ) of in vivo proximal renal tubules, using microperfusion with H ion‐sensitive microelectrodes. In the WKY rats, the mean control value of JHCO 3 − was 2,41 ± 0,12 nmol.cm −2 .s −1 (N=14). Losartan [10 −7 M; an Ang II receptor AT1 antagonist] alone decreased the JHCO 3 − to 1,64 ± 0,09 nmol.cm −2 .s −1 (11); A779 [10 −6 M; an Ang‐(1‐7) receptor Mas antagonist] alone decreased the JHCO 3 − to 1,75 ± 0,08 nmol.cm −2 .s −1 (09). These data indicated that in the basal situation intratubular Ang II and Ang‐(1‐7) stimulates the JHCO 3 − . Ang‐(1‐7) (10 −9 M) injected into luminally perfused tubules causes a significant decrease [to 1,73 ± 0,09 nmol.cm −2 .s −1 (12) but Ang‐(1‐7) (10 −6 M) increases it to 3,00 ± 0,11 nmol.cm −2 .s −1 (18). However, A779 and losartan did not affect the inhibitory effect but prevents the stimulatory effects of Ang‐(1‐7) in JHCO 3 − . S3226 (10 −6 M; an inhibitor of the NHE3 isoform of Na + /H + ) alone decreases JHCO 3 − to 1,19 ± 0,05 nmol.cm −2 .s −1 (14), does not affect the inhibitory effect of Ang‐(1‐7) and changes its stimulatory effect to an inhibitory effect [1,30 ± 0,07 nmol.cm −2 .s −1 (19)]. In the SHR rats, JHCO 3 was 2,00 ± 0,13 nmol.cm −2 .s −1 (09). Losartan alone decreased the JHCO 3 to 1,11 ± 0,07 nmol.cm −2 .s −1 (15); A779 alone decreased the JHCO 3 − to 1,22 ± 0,09 nmol.cm −2 .s −1 (11). These data indicated that in the basal situation endogenous intratubular Ang II and Ang‐(1‐7) stimulate JHCO 3 − . Ang‐(1‐7) (10 −9 M) in luminally perfused tubules causes a significant increase [to 2,50 ± 0,12 nmol.cm −2 .s −1 (24) but Ang‐(1‐7) (10 −6 M) decreased it to 1,40 ± 0,07 nmol.cm −2 .s −1 (08). However, losartan did not affect the inhibitory effect but prevented the stimulatory effect of Ang‐(1‐7) on JHCO 3 − . A779 prevents the inhibitory and the stimulatory effects of Ang‐(1‐7) on JHCO 3 − . S3226 alone decreases the JHCO 3 − to 1,03 ± 0,05 nmol.cm −2 .s −1 (11), does not affect the inhibitory effect of Ang‐(1‐7) and changes its stimulatory effect to an inhibitory effect [0,99 ± 0,09 nmol.cm −2 .s −1 (19)]. So, our data are showing that in WKY and SHR rats, the inhibitory dose‐dependent effect of Ang‐(1‐7) on JHCO 3 − is partially mediated by the AT1 receptor, demonstrating a possible inhibitory beneficial effect of Ang‐(1‐7) in hypertensive rats opposite to the deleterious stimulatory effects of Ang II. It is therefore reasonable to assume that, in the intact animal, the interaction of the opposite dose‐dependent effects of Ang‐(1‐7) and Ang II on the Na + /H + may represent an important physiological regulation in terms of intra‐ and extracellular volume and/or pH changes. Support or Funding Information FAPESP, CNPq, CAPES