Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2017

Diabetes and hypertension differentially affect renal reactive oxygen species and catecholamine content (#41)

Anna MD Watson 1 2 , Sally Penfold 1 , Eleanor AM Gould 2 , Kristy L Jackson 2 , John-Luis Moretti 2 , Putra Riza Pratama 2 , Stephen P Gray 2 , Eikelis N 3 , Gavin W Lambert 2 3 , Geoffrey A Head 1 2 , Karin AM Jandeleit-Dahm 1 2
  1. Monash University, Melbourne, VIC, Australia
  2. Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
  3. Swinburne University of Technology, Melbourne, VIC, Australia

Background: Patients with both diabetes and hypertension develop nephropathy at an accelerated rate. Using the hypertensive Schlager mouse model, we examined changes in renal function, sympathetic nerve status and the oxidative status of the kidney in 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 for 24hr and had kidneys harvested. In a separate group of animals 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). Diabetic BPN and BPH mice showed significantly greater albuminuria than non-diabetic controls, with diabetic BPN showing less albuminuria than diabetic BPH (439 ± 73 vs. 1205 ± 196 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 kidneys from hypertensive mice but interestingly diabetic mice had significantly less renal noradrenaline in both mouse strains. Renal cortical peroxide formation was increased in non-diabetic BPH mice and while activity of the anti-oxidant enzyme 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).

Conclusion: Kidneys of non-diabetic hypertensive mice show greater renal oxidative stress than normotensive mice. While diabetic hypertensive animals have greater oxidative stress they had lower catalase activity, indicating compromised ability to deal with hypertensive lead increases in oxidative stress. This could contribute to greater renal neuropathy, further compromising renal function. This mechanism may underlie the poor outcome for patients with hypertensive diabetic nephropathy.