Intrarenal angiotensin II: Interstitial and cellular levels and site of production

Background. Both local production and angiotensin II subtype 1 (AT(1)) rece ptor-mediated uptake from the circulation contribute to the high levels of angiotensin (Ang) II in the kidney. It is largely unknown where Ang II is p roduced in the kidney and how much of it originates from the circulation. Methods. The concentrations of endogenous and I-125-labeled Ang I and II we re measured in renal tissue and in blood from pigs receiving systemic infus ions of I-125-Ang I. Pigs were either untreated or treated with the angiote nsin converting enzyme (ACE) inhibitor captopril or the AT(1) receptor anta gonist eprosartan. Results. I-125-Ang I was undetectable in renal tissue but the steady-state concentrations of I-125-Ang II in cortical and medullary tissue were four a nd two times the concentration in arterial blood plasma, respectively. The tissue concentrations of endogenous Ang II were 100 and 60 times higher tha n in arterial plasma. Eprosartan reduced I-125-Ang II accumulation by 90%, but did not lower tissue Ang II. Captopril did not alter either I-125-Ang I I accumulation or tissue Ang II. Conclusions. The bulk of Ang II in the kidney is cell-associated. The high tissue/blood concentration ratio of endogenous Ang II may depend on the sam e mechanism as demonstrated for I-125-Ang II, that is, AT(1) receptor-media ted binding to cells and endocytosis. If so, the results indicate that most renal AT(1) receptors are exposed to locally generated Ang II rather than Ang II from the: circulation. We propose the existence of a low-Ang II vasc ular system-related interstitial compartment that is separate from tubular fluid, where, according to micropuncture studies, Ang II levels might be hi gh.