Augmented intrarenal and urinary angiotensinogen in hypertension and chronic kidney disease

Abstract

Activated intrarenal renin-angiotensin system plays a cardinal role in the pathogenesis of hypertension and chronic kidney disease. Angiotensinogen is the only known substrate for renin, which is the rate-limiting enzyme of the renin-angiotensin system. Because the levels of angiotensinogen are close to the Michaelis-Menten constant values for renin, angiotensinogen levels as well as renin levels can control the renin-angiotensin system activity, and thus, upregulation of angiotensinogen leads to an increase in the angiotensin II levels and ultimately increases blood pressure. Recent studies using experimental animal models have documented the involvement of angiotensinogen in the intrarenal renin-angiotensin system activation and development of hypertension. Enhanced intrarenal angiotensinogen mRNA and/or protein levels were observed in experimental models of hypertension and chronic kidney disease, supporting the important roles of angiotensinogen in the development and the progression of hypertension and chronic kidney disease. Urinary excretion rates of angiotensinogen provide a specific index of the intrarenal renin-angiotensin system status in angiotensin II-infused rats. Also, a direct quantitative method has been developed recently to measure urinary angiotensinogen using human angiotensinogen enzyme-linked immunosorbent assay. These data prompted us to measure urinary angiotensinogen in patients with hypertension and chronic kidney disease, and investigate correlations with clinical parameters. This short article will focus on the role of the augmented intrarenal angiotensinogen in the pathophysiology of hypertension and chronic kidney disease. In addition, the potential of urinary angiotensinogen as a novel biomarker of the intrarenal renin-angiotensin system status in hypertension and chronic kidney disease will be also discussed.

Fig. 1

Working scheme for the augmented intrarenal and urinary angiotensinogen in hypertension and chronic kidney disease. Intrarenal renin-angiotensin (Ang) system in proximal and distal nephron segments was summarized. Because of its molecular size, it seems unlikely that much of the plasma angiotensinogen (AGT) filters across the glomerular membrane. In Ang II-dependent hypertension, increased proximal tubular (PT) secretion of AGTspills over into the distal nephron and increases Ang II effects on distal tubular (DT) reabsorption. CD, collecting ducts. ACE, Ang-converting enzyme. AT1, Ang II type 1 receptors adapted from Kobori, 2007 [54]