O'Neill J, Corbett A, Johns EJ. Dietary sodium intake modulates renal excretory responses to intrarenal angiotensin (1-7) administration in anesthetized rats. Am J Physiol Regul Integr Comp Physiol 304: R260 -R266, 2013. First published December 19, 2012 doi:10.1152/ajpregu.00583.2011-Angiotensin II at the kidney regulates renal hemodynamic and excretory function, but the actions of an alternative metabolite, angiotensin (1-7), are less clear. This study investigated how manipulation of dietary sodium intake influenced the renal hemodynamic and excretory responses to intrarenal administration of angiotensin (1-7). Renal interstitial infusion of angiotensin (1-7) 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. By contrast, renal interstitial infusion of angiotensin (1-7) in rats maintained on a high-sodium intake had no effect on glomerular filtration rate, whereas the diuresis and natriuresis was markedly attenuated compared with those in rats fed either a normal or low-sodium diet. Plasma renin and angiotensin (1-7) were highest in the rats on the low-sodium diet and depressed in the rats on a high-sodium diet. These findings demonstrate that the renal hemodynamic and excretory responses to locally administered angiotensin (1-7) is dependent on the level of sodium intake and indirectly on the degree of activation of the renin-angiotensin system. The exact way in which angiotensin (1-7) exerts its effects may be dependent on the prevailing levels of angiotensin II and its receptor expression.angiotensin (1-7); dietary sodium; renal hemodynamics; sodium excretion THE RENIN ANGIOTENSIN SYSTEM (RAS) is a powerful endogenous hormonal cascade that plays a central role in the regulation of blood pressure, sodium balance, and body fluid homeostasis. Classically, this cascade culminates in the formation of the potent vasoconstrictor, antinatriuretic and antidiuretic peptide angiotensin II (ANG II) (7,20). ANG II is produced from angiotensin I (ANG I) primarily via angiotensin-converting enzyme (ACE) but also via the tissue enzyme chymase. The latter has been shown to contribute to the production of ANG II in the diabetic mouse kidney (21). More recently, another RAS peptide called angiotensin (1-7) [ANG (1-7)] has been described as the endogenous counter regulator of ANG II (16) via activation of its "mas" receptor (24). ANG (1-7) is formed directly from ANG II by the ACE isoform ACE 2 (27, 32) but can also be synthesized directly from ANG I via tissue-specific peptidases such as neprilysin in the kidney (2).The intrarenal actions of ANG (1-7) and its interaction with ANG II on renal hemodynamics and tubular fluid reabsorption h...

This study investigated how the renal excretory actions of ANG1–7 were altered when the renin‐angiotensin system (RAS) was activated or suppressed following a period of low or high dietary sodium intake. Male Wistar rats were fed a low (0.03%), normal (0.3%) or a high (3.0%) sodium diet for 2 weeks. The animals were anaesthetised with chloralose/urethane and prepared for the measurement of blood pressure (BP), iv infusion of saline (0.9%NaCl, 3.0 ml/h). Cannulae were placed in the left ureter for urine collection and at the cortico‐medullary border for saline or ANG1–7 infusion at 1.0ml/h. Four 20 min clearances were taken, two before and two 45min after either saline or ANG1–7 (9×10−7M) infusion. Data, means ±SEM were analysed using Student's t test. Infusion of saline had no effect on BP or any renal functional parameter. ANG1–7 infusion in rats on the normal diet did not change BP, at 99±4mmHg, but urine flow, at 18.1±1.3μl/min/kg, and fractional sodium excretion (FENa), at 0.6±0.1, were increased by 24 and 25% (both P<0.05). In the low salt rats, ANG1–7 caused a greater response in FENa, of some 2–3 fold (P<0.05) whereas in the high salt rats, it was blunted, being only 60% of the response in normal rats. These findings demonstrate a dependency of the excretory responses to ANG1–7 on the endogenous levels of RAS.

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