Angiotensin-(1–7) reverts the stimulatory effect of angiotensin II on the proximal tubule Na +-ATPase activity via a A779-sensitve receptor

Abstract

Recently, we demonstrated that the stimulatory effect of Ang II on the Na +-ATPase activity in proximal tubules is reversed, in a dose-dependent manner, by Ang-(1–7) [Biochim. Biophys. Acta 1467 (2000) 189]. In the present paper, we characterized the receptor involved in this phenomenon. The preincubation of the Na +-ATPase with 10 −8 M Ang II increases the enzyme activity from 7.50±0.02 (control) to 12.40±1.50 nmol Pi mg −1 min −1 ( p<0.05). Addition of 10 −9 M Ang-(1–7) completely reverts this effect returning the ATPase activity to the control level. This effect seems to be specific to Ang-(1–7) since Ang III (10 −12–10 −8 M) does not modify the stimulation of the renal proximal tubule Na +-ATPase activity by Ang II. Saralasin abolishes the Ang-(1–7) effect in a dose-dependent manner being the maximal effect obtained at 10 −11 M. The increase in A779 concentration (from 10 −12 to 10 −7 M), a specific Ang-(1–7) antagonist, also abolishes the Ang-(1–7) effect. On the other hand, PD123319 (10 −8–10 −6 M), an AT 2 antagonist receptor, and losartan (10 −12–10 −7 M), an AT 1 antagonist receptor, does not modify the effect of Ang-(1–7). Taken together, these data indicate that Ang-(1–7) reverts the stimulatory effect of Ang II on the Na +-ATPase activity in proximal tubule through a A779-sensitive receptor.