Effect of renin angiotensin system blockade on the islet microvessel density of diabetic rats and its relationship with islet function

Abstract

To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin (30 mg/kg). After 8 weeks intervention with perindopril (AE, n=10) or valsartan (AR, n=10), the islet function of the animals was evaluated by intravenous insulin release test (IVIRT). The pancreases were immunohistochemically stained to analyze the content of insulin and vascular endothelial growth factor (VEGF) in the islets. The microvessel density (MVD) of islets was detected by counting CD34 positive cells. The hypoxia inducible factor (HIF)-1α mRNA expression in the islets was detected by RT-PCR. Compared with normal control group (NC, n=10), the area under the curve for insulin from 0 to 30 min (AUCI_0–30) of diabetes group (DM, n=8) was decreased by 66.3%; the insulin relative concentration (IRC) of βcell was decreased significantly; the relative content of VEGF was increased obviously [(−4.21±0.13) vs (−4.06±0.29)]; MVD in islets was decreased by 71.4%; the relative expression of HIF-1α mRNA was increased by 1.19 times (all P<0.01). Compared with DM group, the AUCI_0-30 of AE and AR group was increased by 44.6% and 34.9% respectively; IRC was also increased significantly; the relative content of VEGF was decreased by 21.2% and 21.7% respectively; MVD was increased by 62.5% and 75.0% respectively; the relative expression of HIF-1α was decreased by 27.2% and 29.0% respectively (all P<0.01 or P<0.05). There were no significant differences in the said indexes between group AE and AR. It is concluded that the blockade of RAS may ameliorate islets function of diabetic rats by increasing the MVD in islets.

Keywords

renin angitotensin system / diabetes mellitus / islet function / microvessel density

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