Kidney Angiotensin II Levels vs. Plasma Angiotensin II Levels
Yes, kidney angiotensin II (Ang II) levels are significantly higher than plasma angiotensin II levels, with renal tissue concentrations reported to be 60-100 times higher than those found in arterial plasma. 1
Evidence for Higher Kidney Angiotensin II Levels
Kidney tissue contains much higher concentrations of Ang II compared to circulating plasma, with studies showing that intrarenal Ang II levels are predominantly regulated by angiotensinogen 2
Research has demonstrated that endogenous Ang II concentrations in kidney tissue are approximately 100 times higher in cortical tissue and 60 times higher in medullary tissue compared to arterial plasma levels 1
The high tissue-to-blood concentration ratio of endogenous Ang II appears to be dependent on AT1 receptor-mediated binding to cells and endocytosis, suggesting a mechanism for the accumulation of Ang II within kidney tissue 1
Mechanisms Behind Elevated Kidney Angiotensin II
The renin-angiotensin system (RAS) functions as a local renal paracrine system, with all components present within the kidney, including angiotensinogen, renin, angiotensin I, angiotensin-converting enzymes, angiotensin II, and angiotensin receptors 3
Ang II is compartmentalized in the renal interstitial fluid at much higher concentrations than those existing in the circulation, creating a localized environment with elevated Ang II levels 2
AT1 receptor-mediated uptake from circulation contributes significantly to the high levels of Ang II in the kidney, with studies showing that AT1 receptor antagonists can reduce labeled Ang II accumulation by up to 90% 1
Interestingly, most of the Ang II in the kidney is cell-associated, suggesting that the majority of renal AT1 receptors are exposed to locally generated Ang II rather than Ang II from circulation 1
Source of Kidney Angiotensin II
Despite the kidney's ability to express angiotensinogen mRNA, research indicates that liver-derived angiotensinogen is actually the primary source of renal angiotensinogen protein and angiotensin II 4
Liver-specific knockout of angiotensinogen nearly abolishes both plasma and renal angiotensinogen protein as well as renal tissue angiotensin II, while kidney-specific angiotensinogen knockout mice maintain normal levels of renal angiotensinogen and Ang II 4
The proximal tubule reabsorbs filtered angiotensinogen through megalin, a process that contributes to the local generation of Ang II within kidney tissue 4
In proteinuric kidney diseases, increased permeability of the glomerular capillary wall to angiotensinogen enhances the synthesis of renal Ang II, further elevating kidney Ang II levels 4
Clinical Implications
The independent regulation of intrarenal RAS and its inappropriate activation contributes to the pathogenesis of hypertension and renal disease 2
Angiotensin-converting enzyme 2 (ACE2) plays a key role in modulating renal Ang II levels, with decreased ACE2 activity associated with increased blood pressure, diabetes, and oxidative stress 5
Therapeutic targets aiming to increase ACE2 activity could potentially become clinically relevant, especially in disease states where the renal RAS is upregulated 5
Understanding the disparity between kidney and plasma Ang II levels is important for developing targeted therapies for renal and cardiovascular diseases 3