Intrarenal Infusion of Angiotensin-(1–7) Modulates Renal Functional Responses to Exogenous Angiotensin II in the Rat

Abstract

In the present study we investigated the possible role of angiotensin-(1–7) [Ang-(1–7)] in modulating renal functional responses to intrarenal (i.e.) infusion of angiotensin II (ANG II) in normotensive anesthetized rats. ANG II (6 ng/min, n = 14) decreased glomerular filtration rate (GFR), renal plasma flow (RPF), absolute and fractional sodium excretion by –24 ± 5, –25 ± 6, –44 ± 6 and –28 ± 7%, respectively (p < 0.05). i.r. infusion of Ang-(1–7) (50 ng/min, n = 13) did not significantly alter GFR (+6 ± 4%) but reduced RPF by –19 ± 7% (p < 0.05). Ang-(1–7) increased absolute and fractional sodium excretion by +36 ± 6 and +37 ± 8%, respectively (p < 0.05). Infusion of Ang-(1–7) did not prevent the decreases in GFR and RPF but completely blunted the decreases in absolute (–2 ± 2%) and fractional sodium excretion (–4 ± 4%) induced by ANG II (n = 11). Blockade of the Ang-(1–7) receptor by [7-D-Ala]-Ang-(1–7) (5 µg/min, n = 11) significantly decreased GFR, RPF, absolute and fractional sodium excretion by –28 ± 7, –20 ± 5, –32 ± 7 and –24 ± 4%, respectively (p < 0.05), suggesting that the action of endogenous ANG II is unopposed by compensatory effect of endogenous Ang-(1–7). i.r. infusion of Ang-(1–7) (n = 10) did not alter the effect of Ang-(1–7) receptor blockade on RPF (–21 ± 6%) but blunted its effects on GFR (+4 ± 3%) and absolute (+7 ± 5%) and fractional (+6 ± 4%) urinary sodium excretion probably by displacing the receptor blocker. While exogenous ANG II during blockade of the Ang-(1–7) receptor and the AT₂ receptor (by PD 123319; 1 µg/min i.r., n = 9) resulted in the same decreases in absolute and fractional sodium excretion (–39 ± 8 and –38 ± 6%, respectively, p < 0.05) as did ANG II in the absence of Ang-(1–7) receptor blockade. These results suggest that in normotensive rats high i.r. Ang-(1–7) concentration attenuates the tubular, i.e. sodium reabsorptive effect, but not the vascular effect of exogenous i.r. ANG II. Results obtained during blockade of Ang-(1–7) and of AT₂ receptors imply that AT₂ receptors play a role in tubular sodium reabsorption in the presence of high ANG II concentration