Capillary endothelial but not lymphatic function is restored under rosiglitazone in Zucker diabetic fatty rats.

If thiazolidinediones have shown beneficial effects on macrovascular endothelial function, their effects on microcirculation and lymphatic function are not well documented. The aim of the study was to assess the effect of rosiglitazone on interstitial albumin retention and lymphatic function in Zucker Diabetic Fatty (ZDF) rats. Three series of 9-14 rats were studied: Lean (fa/?) controls, ZDF (Gmi-fa/fa) rats and ZDF rats treated with rosiglitazone from 8 to 26 weeks of age (ZDF-ROSI). Albumin retention and lymphatic uptake of interstitial albumin (LF/HF ratio) were evaluated on hindquarters with a noninvasive isotopic test using technetium-labelled albumin. Vascular Endothelial Growth Factor (VEGF) was measured. At week 25, albumin retention was markedly higher in ZDF rats (9.9+/-1.0%) than in control rats (1.0+/-0.8%, p<0.001), but did not differ significantly between the ZDF-ROSI group (2.5+/-1.5%) and the control group. LF/HF ratio was similarly increased in the ZDF group (1.14+/-0.07%) and the ZDF-ROSI group (1.07+/-0.04%) as compared to control rats (0.65+/-0.04%; p<0.001 for both). We can deduce that the prevention of the increase of albumin retention under rosiglitazone results from a decrease in the capillary filtration of albumin. VEGF levels were 7.1+/-1.5, 7.3+/-1.9, 3.5+/-1.6 pg/mL in the control, ZDF and ZDF-ROSI groups, respectively (p=0.23). In ZDF rats, rosiglitazone prevents interstitial albumin retention and the increase in capillary filtration of albumin. However lymphatic function is still impaired and might contribute to oedema.

Effect of rosuvastatin on capillary filtration of albumin and blood pressure in rats with streptozotocin-induced diabetes.

An increase in capillary filtration of albumin (CFA) is well demonstrated in diabetes. Statins may exert a protective effect against endothelial dysfunction. The aim of this study was to test whether rosuvastatin may prevent the increase in peripheral CFA in diabetic rats and the role of blood pressure lowering. Rats with streptozotocin-induced diabetes were randomized to receive either rosuvastatin 20mg/kg/d (group R) or both rosuvastatin 20mg/kg/d and mevalonate 20mg/kg/d (group RM) or no treatment (group U). CFA index was measured on a limb by a non-invasive isotopic test using technetium-labelled albumin, at three time points: at mean age of 3 months, before treatment; at 5 and 8 months, i.e. after 2 and 5 months of treatment. At 3 months, interstitial albumin retention (AR) was markedly increased in the 3 groups. From 3 to 5 months, AR increased significantly in group U, decreased in group R and in group RM. At 5 and 8 months, AR was significantly lower in groups R and RM than in group U. Systolic blood pressure (SBP) was measured at 8 months and was significantly lower in group R than in group U and RM. At 8 months, serum cholesterol levels were not different between the three groups whereas triglycerides were significantly lower in groups R and RM than in group U. In conclusion, in diabetic rats rosuvastatin prevents the increase in peripheral CFA and induces a decrease in blood pressure. The beneficial effect of rosuvastatin on endothelial function does not seem to result from blood pressure reduction nor lipid lowering effects.