A WATSON1, P PRATAMA1, S PENFOLD1, E GOULD2, S GRAY2, G LAMBERT3, G HEAD2, K JANDELEIT-DAHM1
1Department Of Diabetes, Monash University, Melbourne, Australia, 2Baker Heart and Diabetes Institute, Melbourne, Australia, 3Swinburne University of Technology, Melbourne, Australia
Aims: To examine changes in renal function, sympathetic nerves and the oxidative status of the kidney in diabetic mice with and without concomitant hypertension.
Background: Patients with both diabetes and hypertension develop nephropathy at an accelerated rate. Using the hypertensive Schlager mouse as a model, we examined changes in the kidney from diabetic mice with and without concomitant hypertension.
Methods: After 10 weeks of study, hypertensive BPH/2J and normotensive BPN/3J Schlager mice with and without concomitant streptozotocin induced diabetes (5x 55 mg/kg i.p.) were placed in metabolic cages (24hr) before kidneys were harvested; alternatively BP telemetry probes were implanted.
Results: Induction of diabetes did not change the hypertensive status of BPH mice (MAP 131±4 vs. 129±4 mmHg for non-diabetic vs. diabetic BPH, n=5 &6). Diabetes induced albuminuria in both strains however diabetic BPH showed significantly greater albuminuria than diabetic BPN (1205±196 vs. 439±73 μg/24hr, n=8, 7). Plasma cystatin C was significantly lower in diabetic animals with no difference between strains. HPLC measurement of cortical noradrenaline showed significantly greater levels in BPH mice. Diabetic mice of both strains had significantly less renal noradrenaline. Renal cortical hydrogen peroxide formation was increased in non-diabetic BPH mice. While activity of catalase was increased in non-diabetic BPH mice it was significantly less in diabetic BPH animals (non-diabetic vs. diabetic BPH 104±8 vs. 63±6 nmol/min/ml, n=8/gp).
Conclusions: Hypertensive mice show greater renal oxidative stress than normotensive mice however diabetic hypertensive animals also demonstrated lower catalase activity, indicating a compromised ability to deal with hypertensive lead increases in oxidative stress. This could contribute to greater renal neuropathy and which may underlie the poor outcome for patients with hypertensive diabetic nephropathy.
Biography:
After working in autonomic neurobiology at the Florey Institute (Melbourne) and at the German Institute for Human Nutrition (Potsdam, German) Anna Watson completed her PhD at the Florey Institute investigating neural and humoral control of the heart. She then moved into the field of diabetic cardiovascular and renal complications (Baker Institute, Melbourne) before moving to the newly formed Department of Diabetes (Monash University). She is currently investigating the role of neural signalling in the development of diabetic nephropathy and hypertension.