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

Abstract

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, insensitive 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 increase in V max, while the apparent affinity of the enzyme for Na + is not modified. Saralasin, a general angiotensin receptor antagonist, abolishes the stimulation, demonstrating that the Ang-(1–7) effect is mediated by receptor. 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 antagonist losartan from 10 −11 to 10 −9 M, reverses the Ang(1–7) stimulation completely. A further increase to 10 −3 M losartan reverses the Na +-ATPase activity 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 angiotensin II (AG II) alone. However, when the two peptides are both present, Na +-ATPase activity is restored to control values. These data suggest that Ang-(1–7) selectively modulates the Na +-ATPase activity present in basolateral membranes of kidney proximal tubules through a losartan-sensitive receptor. This receptor is probably different from the receptor involved in the stimulation of the Na +-ATPase activity by angiotensin II.