Intrarenal production of angiotensin II.

The intrarenal renin-angiotensin system plays a critical role in the paracrine regulation of renal hemodynamics and tubular transport function. Much of the intrarenal angiotensin II (ANG II) is formed locally as evidenced by intrarenal ANG II contents that are much greater than can be explained from the circulating ANG II concentration. Intrarenal ANG II is formed from systemically delivered ANG I and from intrarenally formed ANG I derived from systemically delivered angiotensinogen as well as locally synthesized angiotensionogen. There is a regional distribution of intrarenal ANG II in that the medullary content per gram of tissue is four to five times higher than the cortical content. In addition, most of the cortical ANG II is compartmentalized in the renal interstitial fluid and in the tubular fluid. Proximal tubule cells contain all the components of the renin-angiotensin system necessary for synthesis and secretion of ANG II. Proximal tubule concentrations of ANG II as well as ANG I and angiotensinogen support the concept that the proximal tubule cells secrete ANG II or precursors of ANG II into the tubular fluid. The intratubular concentrations of ANG II are in the nanomolar range, indicating a substantial capability to influence luminal ANG II receptors on the tubule cell membranes. Thus, much of the ANG II-dependent actions on tubular transport functions could be due to specific effects of locally synthesized ANG II on luminal ANG II receptors. Experimental evidence shows that the intratubular ANG II concentrations are regulated independently of the circulating concentrations, but the specific mechanisms responsible remain to be delineated.