Effects of angiotensin II receptor antagonist olmesartan on renal hemodynamic variables and vascular structural properties in streptozotocin-induced diabetic rats.

BACKGROUND

Diabetic nephropathy is a major cause of renal failure in diabetes mellitus (DM). It has been known that renin-angiotensin system (RAS) blockers have a renal protective effect. This study aimed to investigate whether treatment with angiotensin II receptor blocker, olmesartan, could modify renal hemodynamic variables and vascular structural properties, then attenuate renal injury in streptozotocin (STZ)-induced DM rats.

METHODS

DM was induced in male Wistar rats by intraperitoneal administration of STZ. The rats were then randomized to a DM group and an olmesartan treatment (OLM + DM) group. The normal group (non-DM) were administered only citrate buffer. At the end of the 14th week, blood glucose, kidney weight/body weight and urinary protein-to-creatinine ratio were determined. Further, the flow-pressure and pressure-glomerular filtration rate (GFR) relationships were determined for maximally vasodilated, perfused kidneys. From the relationship, 3 indices of vascular structural properties were estimated: slope of flow-pressure (minimal renal vascular resistance, reflecting overall luminal dimensions of preglomerular and postglomerular vasculature), slope of pressure-GFR (glomerular filtration capacity against pressure) and threshold pressure for beginning filtration at pressure-GFR (preglomerular to postglomerular vascular resistance ratio). Kidneys were then perfusion fixed for histological analysis. The renal histopathology was observed by light microscopy.

RESULTS

The body weight of DM rats was lower than that of non-DM rats. Blood glucose, kidney weight/body weight, urinary protein-to-creatinine ratio were significantly greater in DM rats than in non-DM rats. The parameters such as kidney weight/body weight, urinary protein-to-creatinine ratio in OLM + DM rats had dramatically decreased compared with those in DM rats. However, the treatment with olmesartan had no effect on blood glucose levels. The slope of flow-pressure relationship was greater in DM rats than that in non-DM rats (P < 0.05). But the slope of the pressure-GFR relationship was lower in DM rats than that in non-DM rats (P < 0.05) with the x-intercept of the line similar between the two groups. The slope of the flow-pressure relationship was decreased in DM rats group treated with olmesartan (P < 0.05). Moreover, olmesartan significantly increased the slope of the pressure-GFR relationship in DM rats (P < 0.05). The x-intercept of the pressure-GFR relationship reduced following olmesartan in DM rats.

CONCLUSIONS

Treatment with olmesartan reduced urinary protein-to-creatinine ratio independent of blood glucose and increased average renal vessel lumen diameter in the perfused kidneys of STZ-induced DM rats, predominantly in preglomerular vessels, and then improved renal excretory capability. These findings were consistent with remodeling of the preglomerular vasculature in our hisological measurements.