Why are angiotensin concentrations so high in the kidney?
OBJECTIVE
Recent studies have reported that intrarenal angiotensin II content and angiotensin II concentrations in the proximal tubular fluid and renal interstitial fluid are much greater than the circulating angiotensin II levels. These high intrarenal angiotensin II levels are responsible for regulating renal hemodynamics and tubular transport.


RESULTS
Intrarenal angiotensin II levels have been assessed from total tissue contents as well as renal interstitial fluid and proximal tubular fluid concentrations. Total tissue contents expressed per gram of tissue weight are greater than plasma angiotensin II concentrations; tubular fluid concentrations and renal interstitial fluid concentrations are even greater in the range of 3-10 pmoles/ml. In hypertensive states, there is also an increased intracellular accumulation of angiotensin II mediated by angiotensin type 1 receptor-dependent endocytosis. The high intrarenal angiotensin II levels are also caused by the presence of angiotensinogen messenger RNA and protein in the proximal tubule cells. Furthermore, there is positive amplification by which increases in circulating angiotensin II stimulate increased production and secretion of angiotensinogen, which is also manifested as an increased urinary excretion rate.


CONCLUSIONS
The ability of the kidney to generate high intratubular and interstitial concentrations allows the kidney to regulate intrarenal levels in accord with the homeostatic needs for the regulation of renal hemodynamics and tubular reabsorption and the regulation of sodium balance. When inappropriately stimulated, high intrarenal angiotensin II levels contribute to excessive salt and water retention, the development of hypertension, and long-term proliferative effects leading to renal injury.
Navar
L Gabriel
LG
Department of Physiology and Hypertension, Renal Center of Excellence, Tulane University Health Scences Center, New Orleans, Louisiana 70112, USA. navar@tulane.edu
Nishiyama
Akira
A
D000804:Angiotensin II / Q000378:metabolism; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D045604:Extracellular Fluid / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D014018:Tissue Distribution
D000809:Angiotensins; D000804:Angiotensin II