Hypertension induces oxidative stress but not macrophage infiltration in the kidney in the early stage of experimental diabetes mellitus.
BACKGROUND: The combination of diabetes and hypertension increases the incidence and severity of kidney disease in an additive manner. Inflammatory and oxidative stress mechanisms contribute to renal damage in both diabetes and hypertension. Therefore, we investigated whether renal macrophage infiltration and oxidative stress events are additive from the beginning in diabetic animals with coexisting hypertension. METHODS: Diabetes was induced in spontaneously hypertensive rats (SHRs) and their genetically normotensive control Wistar Kyoto (WKY) rats by streptozotocin injection at 12 weeks of age for 10 days, and the effects of hyperglycemia on renal macrophage infiltration and oxidative stress were evaluated. RESULTS: Blood pressure was higher in SHR than in WKY groups. Markers of oxidative stress-induced DNA and protein modification, 8-hydroxy- 2'-deoxyguanosine (8-OHdG) and nitrotyrosine, respectively, and the antioxidant glutathione levels were found to be similar in WKY-control and WKY-diabetic groups. However, 8-OHdG was significantly elevated (p = 0.014), the nitrotyrosine level tended to be elevated (p = 0.068) and the glutathione level was significantly reduced (p = 0.034) in the SHR-diabetic group compared to the SHR-control group. On the other hand, glomerular and tubulointerstitial macrophage infiltration was significantly higher in both WKY-diabetic and SHR-diabetic groups than the respective control groups. CONCLUSIONS: A short duration of diabetes mellitus induces renal oxidative stress in the presence of hypertension; however, renal macrophage infiltration becomes evident in early diabetes regardless of the presence or absence of hypertension. We conclude that the combination of diabetes and hypertension adversely affects oxidative stress in the kidney, but the combination has no additive effect on renal macrophage infiltration, at least in early diabetes.