Renal Functional Responses to Angiotensin 1‐7 (Ang1‐7) in the Spontaneously Hypertensive Rat (SHR)

Abstract

There is evidence that the natriuretic and diuretic actions of Ang1‐7 are dependent on the degree of activation of the renin angiotensin system but it is uncertain whether they are independent of blood pressure. This study examined the effect of intra‐renal infusion of Ang1‐7 on sodium and water excretion in SHR and normotensive Wistar rats, in which both strain's plasma renin and angiotensin II are similar. Twelve week old male Wistar or SHRs (n=7) were anaesthetised and prepared for measurement of mean arterial pressure (MAP), glomerular filtration rate (GFR), urine flow (UV) and fractional sodium excretion (FENa). Clearances, of 20 min, were taken before and during the intra‐renal infusion of saline or Ang1‐7 (3x10‐3M) at 1ml/h. Means±SEM were compared (Wilcoxon matched pairs) and significance taken at P<0.05. Intra‐renal Ang1‐7 infusion did not change MAP or GFR in either SHR or Wistar groups, at 172±9 and 113±6mmHg and 3.4±0.3 and 4.8±0.2ml/min/kg respectively. UV and FENa increased from 57.5±11.1 to 69.3±9.1µl/min/kg and 1.6±0.3 to 2.5±0.3% (P<0.05) in the SHR group and from 96.0±3.9 to 132.1±8.1µl/min/kg and from 1.8±0.1 to 2.3±0.1% (P<0.05) in the Wistar group. These responses were not significantly different across the groups. These findings showed that Ang1‐7 infusion into the kidney caused a diuresis and natriuresis, the magnitude of which was indistinguishable between SHR and normotensive Wistar rats. They indicate that the elevated MAP in the SHR does not contribute to the magnitude of the excretory responses. The data further support the view that the natriuretic and diuretic actions of Ang1‐7 are dependent on the status of the endogenous renin‐angiotensin system but are independent of blood pressure.