Intrarenal infusion of angiotensin-(1-7) modulates renal functional responses to exogenous angiotensin II in the rat
Abstrakt
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) Accepted: February 4, 2002 receptor by [7-D-Ala]-Ang-(1-7) (5 mug/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 AT(2) receptor (by PD 123319; 1 mug/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 AT(2) receptors imply that AT(2) receptors play a role in tubular sodium reabsorption in the presence of high ANG II concentration.