Renin and angiotensinogen expression during the evolution of diabetes.

Abstract

The expression of renin and angiotensinogen genes and their proteins were studied daring the progression of diabetes using adult BioBreeding spontaneously diabetic rats at 1 day and 2-12 months of diabetes. The number of renin-stained cells per juxtaglomerular apparatus was determined by immunocytochemistry. Initially, at 2 months of diabetes the number of renin-stained cells per juxtaglomerular apparatus increased significantly (p< 0.0001,2 months versus resistant groups) and was followed by a decrease in the number and intensity of renin-stained cells after 12 months of diabetes (/>=0.007, 2 months versus 12 months). A significant negative correlation was observed between the number of renin-containing cells and the duration of diabetes (r=0.99,p=0.014). Immunoreactive angiotensinogen was restricted to the proximal tubule and appeared increased after 4 and 8 months of diabetes as compared with the 2-and 12-month diabetic groups. Renin messenger RNA (mRNA) levels increased with the onset of diabetes and decreased markedly during chronic diabetes. At 1 day of diabetes, renin mRNA levels were 700% higher than at 12 months of diabetes. Angiotensinogen mRNA levels were unchanged. We conclude that diabetes results in an initial increase in renin gene expression, and as the duration of diabetes lengthens, there is a progressive decrease in renin gene expression and in the number of cells containing renin. These findings suggest that as the duration of diabetes and the age of the animal lengthens, there is a decrease in the number of cells expressing the renin gene. Physiological studies using the streptozocin rat model have suggested that the altered glomerular hemodynamics, namely, increased glomerular capillary pressure and decreased ultrafiltration coefficient, seen in diabetes are responsible for subsequent glomerular injury and decreased renal function.3 Angiotensin converting enzyme inhibition corrects the glomerular hemodynamic changes observed in diabetes and may arrest the progression of glomerular damage and renal

Inhibition of diabetic nephropathy by a decoy peptide corresponding to the “handle” region for nonproteolytic activation of prorenin

“…The kidney Ang I and II content was similar among the C, C + HRP, and DM + HRP rats. The kidney ACE and angiotensinogen mRNA levels were similar in the C, C + HRP, DM, and DM + HRP rats during the 24-week treatment period, consistent with previous studies (17)(18)(19) (Figure 7, B and C).…”

“…Previous studies showed that kidney renin mRNA levels increased at the early onset of diabetes in spontaneously or streptozotocin-induced diabetic rats (13,17,19,21) and decreased markedly thereafter (17). The present study demonstrated that both the total kidney renin (proteolytically activated and prorenin) content and kidney renin mRNA level were lower in the DM rats than in the C rats at 12 and 20 weeks of age (8 and 16 weeks of diabetes) when the nephropathy develops, and they were similar at 28 weeks of age (24 weeks of diabetes) when the nephropathy progresses.…”

The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease

“…Treatment with an ACEI prevented increases in intrarenal Ang II and reversed manifestations of diabetic nephropathy (Sharma et al, 2006). The BioBreeding spontaneously diabetic rats showed an initial increase in renin gene expression, although there was a progressive decrease in renin gene expression and in the number of cells containing renin as the duration of diabetes lengthened (Everett et al, 1992) Streptozotocin destroys pancreatic ␤ cells and induces type 1 diabetes mellitus. In streptozotocin-induced diabetic rats, an increase in renal renin mRNA and protein content was demonstrated (Anderson et al, 1993).…”

Tissue Gene Expression of Renin-Angiotensin System in Human Type 2 Diabetic Nephropathy

“…First, renal tissue angiotensin II concentration has been variously reported to be increased (19,20), to be comparable (21), and to be decreased (22) compared with nondiabetic kidney. With respect to the gene expressions of RAS in the animal model kidney, renin expression is reportedly increased at the beginning of the disease (19,23,24) but decreased at the late stage (20,23). Renal tissue AGT expression was reported to be comparable (20,23,25).…”