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

Background. Both local production and angiotensin II subtype 1 (AT(1)) receptor-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 produced 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 were measured in renal tissue and in blood from pigs receiving systemic infusions of I-125-Ang I. Pigs were either untreated or treated with the angiotensin converting enzyme (ACE) inhibitor captopril or the AT(1) receptor antagonist 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 and two times the concentration in arterial blood plasma, respectively. The tissue concentrations of endogenous Ang II were 100 and 60 times higher than 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 II 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 same mechanism as demonstrated for I-125-Ang II, that is, AT(1) receptor-mediated 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 vascular system-related interstitial compartment that is separate from tubular fluid, where, according to micropuncture studies, Ang II levels might be high.