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.

Downregulation of the Vascular Renin-Angiotensin System by Aerobic Training – Focus on the Balance Between Vasoconstrictor and Vasodilator Axes –

“…Indeed, previous studies have shown that the angiotensinogen gene plays a pivotal role in setting blood pressure levels and that angiotensinogen is involved in both intrarenal RAS activation and development of hypertension. 39, 40 Therefore, it is likely that training-induced angiotensinogen reduction in the renal artery is one important mechanism contributing to smaller vasoconstriction and blood pressure fall. Similar observations were previously made in trained vs. sedentary SHR: cardiovascular effects of Ang II were directly correlated with the reduction of Aogen mRNA expression in brain areas involved in cardiovascular control, 13 an effect similar to that observed after chronic losartan treatment.…”

Acute Kidney Injury: Tubular Markers and Risk for Chronic Kidney Disease and End-Stage Kidney Failure

“…An animal study shows that spironolactone treatment in animals with AKI reduces progression to CKD [92] . Elevated urinary angiotensinogen marks intrarenal RAS activation and CKD progression [93][94][95] . Animal studies show that intrarenal angiotensin II increases after renal ischemia reperfusion injury, while concentrations of angiotensin 1-7 (inhibitory molecule to angiotensin II) decrease in the kidney tissues [96] .…”

Glomerular Angiotensin-Converting Enzyme 2 in Pediatric IgA Nephropathy

“…While it is known that angiotensin II (Ang II) is the most powerful biologically active product of the RAS, recent studies have focused on the tissue-specific roles of this system [2,3]. Emerging evidence has demonstrated the importance of the RAS in brain, heart, adrenal glands, vasculature, and kidneys [4]. Angiotensin-converting enzyme (ACE) catalyzes the conversion of angiotensin I (Ang I) to Ang II [5].…”