Journal
AMERICAN JOURNAL OF HYPERTENSION
Volume 19, Issue 5, Pages 541-550Publisher
OXFORD UNIV PRESS
DOI: 10.1016/j.amjhyper.2005.11.014
Keywords
angiotensinogen; kidney; hypertension; diabetic nephropathy; immunoglobulin A nephropathy; radiation nephropathy
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Funding
- NCRR NIH HHS [P20 RR017659, P20RR017659] Funding Source: Medline
- NHLBI NIH HHS [R01HL026371, R01 HL026371] Funding Source: Medline
- NIDDK NIH HHS [R01 DK072408, R01 DK072408-01A1] Funding Source: Medline
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Recent findings related to the renin-angiotensin system have provided a more elaborated understanding of the pathophysiology of hypertension and kidney diseases. These findings have led to unique concepts and issues regarding the intrarenal renin-angiotensin system. Angiotensinogen is the only known substrate for renin that is the rate-limiting enzyme of the renin-angiotensin system. Because the level of angiotensinogen in human beings is close to the Michaelis-Menten constant value for renin, changes in angiotensinogen levels can control the activity of the renin-angiotensin system, and its upregulation may lead to elevated angiotensin peptide levels and increases in blood pressure. Enhanced intrarenal angiotensinogen mRNA or protein levels or both have been observed in multiple models of hypertension including angiotensin II-dependent hypertensive rats, Dahl salt-sensitive hypertensive rats, and spontaneously hypertensive rats, as well Lis in kidney diseases including diabetic nephropathy, immunoglobulin A (IgA) nephropathy, and radiation nephropathy. Renal angiotensinogen is formed primarily in proximal tubular cells and is secreted into the tubular fluid. Urinary angiotensinogen excretion rates show a clear relationship to kidney angiotensin It contents and kidney angiotensinogen levels, suggesting that urinary angiotensinogen may serve as an index of the intrarenal renin-angiotensin system status. Establishment of concise and accurate methods to measure human angiotensinogen may allow clinical studies that would provide important information regarding the roles of intrarenal angiotensinogen in the development and progression of hypertension and kidney diseases.
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