Abstract 240: Blood Pressure, Renal Function and Hemodynamic Responses to Systemic Ang1-7 in Rats Infused Chronically With Ang Ii: Does the Ang1-7 Natriuretic Effect Depend on Renal Hemodynamics?

Abstract

Angiotensin II (AngII) is the primary effector of the renin-angiotensin system (RAS) eliciting hypertensinogenic effects. The final levels of AngII depend on AngII synthesis by angiotensin-converting enzyme (ACE) and its degradation to Ang1-7 by carboxypeptidase (ACE2) and to AngIII by aminopeptidase A. Ang 1-7 exerts natriuretic effects and counteracts some of the actions of increased AngII. The downregulation of ACE2 protein in the kidneys of hypertensive rats suggests that reduced Ang1-7 may play a role in the overall blood pressure, renal hemodynamic and excretory responses to chronic AngII infusion. In the present study, we examined the effects of systemic Ang1-7 infusions on blood pressure, renal hemodynamics and urinary excretion in male Sprague-Dawley rats subjected to chronic AngII infusion (80ng/min) for 14 days (N=8) and in control (N=6) rats. We examined if the natriuretic activity is associated with renal hemodynamic changes and if it is modified by RAS activation in the AngII infused rats. In surgically prepared rats, Ang1-7 was infused systemically at a dose of 110 fmol/min. Systemic Ang1-7 infusion increased MABP slightly at 60-120 min of infusion in both control and AngII infused rats (114±3 to 123±4 and 140±6 to 148 ±7 mmHg; p<0.05). RBF significantly decreased in both control and AngII infused rats (7.5±0.9 to 6.4±1 and 9.5 ±1.3 to 8.4±1; p<0.05). Ang1-7 infusion also decreased MBF in control rats, but not in AngII infused rats (124±22 to 113±19 PU, p<0.05). Acute Ang1-7 infusion significantly increased urine flow predominantly in rats that received AngII infusion (5.2±0.4 to 15.6±3.5 μl/min; p<0.05). Sodium excretion was enhanced in control rats (0.14±0.08 to 0.94±0.3 μmol/min; p<0.05) as well as in those chronically infused with AngII (0.04±0.02 to 0.42±0.1; p<0.05). These changes were observed despite the decreases in RBF and MBF. The results indicate that the decreased Ang1-7 levels observed in hypertensive rats chronically infused with AngII do not contribute to the alterations in renal hemodynamics. However, the natriuretic actions of Ang1-7 may exert opposing effects on tubular transport.