Angiotensin-(1-7) modulates the ouabain-insensitive Na+-ATPase activity from basolateral membrane of the proximal tubule

Angiotensin-(1-7) (Ang-(1-7)) modulates the Na+-ATPase, but not the Na+,K+- ATPase activity present in pig kidney proximal tubules. The Na+-ATPase, ins ensitive to ouabain, but sensitive to furosemide, is stimulated by Ang-(1-7 ) (68% by 10(-9) M), in a dose-dependent manner. This effect is due to an i ncrease in V-max, while the apparent affinity of the enzyme for Nat is not modified. Saralasin, a general angiotensin receptor antagonist, abolishes t he stimulation, demonstrating that the Ang-(1-7) effect is mediated by rece ptor. The Ang-(1-7) stimulatory effect is not changed by either PD 123319, an AT(2) receptor antagonist, or A779, an Ang-(1-7) receptor antagonist. On the other hand, increasing the concentration of the AT(1) receptor antagon ist losartan from 10(-11) to 10(-9) M, reverses the Ang(1-7) stimulation co mpletely. A further increase to 10(-3) M losartan reverses the Na+-ATPase a ctivity to a level similar to that obtained with Ang-(1-7) (10-9 M) alone. The stimulatory effect of Ang-(1-7) at 10-9 M is similar to the effect of a ngiotensin II (AG II) alone. However, when the two peptides are both presen t, Na+-ATPase activity is restored to control values. These data suggest th at Ang-(1-7) selectively modulates the Na+-ATPase activity present in basol ateral membranes of kidney proximal tubules through a losartan-sensitive re ceptor. This receptor is probably different from the receptor involved in t he stimulation of the Na+-ATPase activity by angiotensin II. (C) 2000 Elsev ier Science B.V. All rights reserved.