Activation of the Renin-Angiotensin System by a Low Salt Diet Does Not

36 In angiotensin II (Ang II) infusion hypertension, there is an augmentation of intratubular 37 angiotensinogen (AGT) and Ang II leading to increased urinary AGT and Ang II excretion rates 38 associated with tissue injury. However, the changes in urinary AGT and Ang II excretion rates 39 and markers of renal injury during physiologically induced stimulation of the renin-angiotensin 40 system (RAS) by a low salt diet remain unclear. Male Sprague-Dawley rats received low salt diet 41 (0.03% NaCl, n = 6) and normal salt diet (0.3% NaCl, n = 6) for 13 days. Low salt diet rats had 42 markedly higher plasma renin activity and plasma Ang II levels. Kidney cortex renin mRNA, 43 kidney AGT mRNA and AGT immunoreactivity were not different; however, medullary renin 44 mRNA, kidney renin content and kidney Ang II levels were significantly elevated by the low salt 45 diet. Kidney renin immunoreactivity was also markedly increased in juxtaglomerular apparati 46 (JGA) and in cortical and medullary collecting ducts. Urinary AGT excretion rates and urinary 47 Ang II excretion rates were not augmented by the low salt diet. The low salt diet caused mild 48 renal fibrosis in glomeruli and the tubulointerstitium, but no other signs of kidney injury were 49 evident. These results indicate that, in contrast to the response in Ang II infusion hypertension, 50 the elevated plasma and intrarenal Ang II levels caused by physiological stimulation of RAS are 51 not reflected by increased urinary AGT or Ang II excretion rates or the development of renal 52 injury. 53 54 55 56 57