Intracellular formation and release of angiotensins from juxtaglomerular cells

Evidence accumulates that intrarenal angiotensin II (Ang II) plays important roles in the regulation of renal functions. To determine the mechanism and site of the intrarenal formation of Ang II, we employed histochemical, cell biological and ex vivo perfusion methods. Immunohistochemical studies have revealed the co-existence of renin and Ang II in juxtaglomerular (JG) cells, and electron microscopic studies and subcellular organelle fractionation have demonstrated the localization of renin and angiotensin in renin granules. Cloned and cultured renin-containing cells derived from rat kidney were also found to contain renin, ACE, and Ang I and Ang II. The subcellular fractionation of renin granules from rat kidney homogenate demonstrated the presence of Ang I and Ang II in the renin granule fractions. The findings suggest the formation of both angiotensins in JG cells. To study the release of Ang I and Ang II, we determined the release of these peptides from isolated rat kidney perfused with Krebs-Ringer buffer at a constant pressure. Release of both peptides was stable for as long as two hours in the absence of angiotensinogen in the perfusion medium. There was a positive correlation between renin secretion rate and Ang I secretion rate, and also between Ang I secretion rate and Ang II secretion rate. Since the perfusate does not contain angiotensinogen, these results lead to the hypothesis that Ang II is formed in JG cells in the kidney and is directly secreted with renin into plasma or the interstitial fluid, and that Ang II formed in the kidney cells may participate in various renal functions along with Ang II produced in the plasma.