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

Angiotensin‐(1‐7): Pharmacology and New Perspectives in Cardiovascular Treatments

“…These effects were not dependent upon the AT 1 or AT 2 receptors, but they were attenuated by the Ang-(1-7) antagonist, D-Ala 7 -Ang-(1-7), suggesting involvement of the mas receptor. Interestingly, Ang-(1-7) attenuated the sodium reabsorption caused by Ang II infusion, but the heptapeptide did not affect the Ang IImediated decrease in GFR (Burgelova et al 2002). Clark et al (2003) later showed that this may be caused by the ability of Ang-(1-7) to reduce renal Ang II receptors.…”

Dietary sodium intake modulates renal excretory responses to intrarenal angiotensin (1–7) administration in anesthetized rats

“…However, low doses of ANG (1-7) were found to inhibit and high doses to stimulate fluid transport in cultured renal epithelial cells (3) and in isolated rat proximal convoluted tubules (11). Despite these conflicting reports some in vivo studies have demonstrated that the intrarenal infusion of ANG (1-7) increased sodium and water excretion in dogs (12) and rats (5,6,11).…”

“…-Angiotensin II at the kidney regulates renal hemodynamic and excretory function, but the actions of an alternative metabolite, angiotensin (1)(2)(3)(4)(5)(6)(7), are less clear. This study investigated how manipulation of dietary sodium intake influenced the renal hemodynamic and excretory responses to intrarenal administration of angiotensin (1)(2)(3)(4)(5)(6)(7).…”

“…This study investigated how manipulation of dietary sodium intake influenced the renal hemodynamic and excretory responses to intrarenal administration of angiotensin (1)(2)(3)(4)(5)(6)(7). Renal interstitial infusion of angiotensin (1)(2)(3)(4)(5)(6)(7) in anesthetized rats fed a normal salt intake had minimal effects on glomerular filtration rate but caused dose-related increases in urine flow and absolute and fractional sodium excretions ranging from 150 to 200%. In rats maintained for 2 wk on a low-sodium diet angiotensin (1-7) increased glomerular filtration rate by some 45%, but the diuretic and natriuretic responses were enhanced compared with those in rats on a normal sodium intake.…”

ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

“…Hence, it is also possible that ANG-(1-7) induces diuresis and natriuresis by inhibiting renal tubular Na+/K+-ATPase [174,175]. However, ANG-(1-7) also induced antidiuresis in water-loaded rodents (258) and increased renal tubular sodium reabsorption in rats [176]. In addition, in normal and hypertensive rats [177] and in water-loaded [178] or virgin female rats [179], ANG-(1-7) had an antidiuretic effect that was mediated, at least in part, by the Mas receptor.…”