Intrarenal angiotensin II: interstitial and cellular levels and site of production.
BACKGROUND
Both local production and angiotensin II subtype 1 (AT1) 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 125I-labeled Ang I and II were measured in renal tissue and in blood from pigs receiving systemic infusions of 125I-Ang I. Pigs were either untreated or treated with the angiotensin converting enzyme (ACE) inhibitor captopril or the AT1 receptor antagonist eprosartan.


RESULTS
125I-Ang I was undetectable in renal tissue but the steady-state concentrations of 125I-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 125I-Ang II accumulation by 90%, but did not lower tissue Ang II. Captopril did not alter either 125I-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 125I-Ang II, that is, AT1 receptor-mediated binding to cells and endocytosis. If so, the results indicate that most renal AT1 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.
van Kats
J P
JP
Cardiovascular Research Institute Erasmus University Rotterdam (COEUR), Department of Internal Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
Schalekamp
M A
MA
Verdouw
P D
PD
Duncker
D J
DJ
Danser
A H
AH
D000179:Acrylates / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D013552:Swine; D013876:Thiophenes; D014018:Tissue Distribution
D000179:Acrylates; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D013876:Thiophenes; D000804:Angiotensin II; C068373:eprosartan; D002216:Captopril