AUTHOR=Watson Anna M. D. , Gould Eleanor A. M. , Penfold Sally A. , Lambert Gavin W. , Pratama Putra Riza , Dai Aozhi , Gray Stephen P. , Head Geoffrey A. , Jandeleit-Dahm Karin A. 

TITLE=Diabetes and Hypertension Differentially Affect Renal Catecholamines and Renal Reactive Oxygen Species

JOURNAL=Frontiers in Physiology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2019.00309

DOI=10.3389/fphys.2019.00309

ISSN=1664-042X

ABSTRACT=Patients with diabetic hypertensive nephropathy have accelerated disease progression. Diabetes and hypertension have both been associated with changes in renal catecholamines and reactive oxygen species. With a specific focus on renal catecholamines and oxidative stress we examined a combined model of hypertension and diabetes using normotensive BPN/3J and hypertensive BPH/2J Schlager mice.
Induction of diabetes (5x 55 mg/kg i.p.) did not change the hypertensive status of BPH/2J mice (telemetric 24hr avg. MAP, non-diabetic 131 ± 2vs. diabetic 129 ± 1, n.s at 9 weeks of study). Diabetes-associated albuminuria was higher in BPH/2J vs. diabetic BPN/3J (1205 +196/-169 versus 496 +67/-59 μg/24hr, p=0.008). 
HPLC measurement of cortical norepinephrine and dopamine showed significantly greater levels in hypertensive mice whilst diabetes was associated with significantly lower catecholamines levels in both strains. Diabetic BPH/2J retained greater levels than diabetic BPN/3J (diabetic: norepinephrine BPN/3J 40±4, BPH/2J 91±5, p=0.010; dopamine: BPN/3J 2±1; BPH/2J 3±1 ng/mg total protein, p>0.001 after 10 weeks of study). Diabetic BPH/2J showed greater cortical tubular immunostaining for monoamine oxidase A and cortical hydrogen peroxide formation was greater in both diabetic and non-diabetic BPH/2J. While catalase activity was greater in non-diabetic BPH/2J it was significantly lower in diabetic BPH/2J (cytosolic: BPH/2J 127±12 vs. 63±6 nmol/min/ml, p<0.001).
We conclude that hypertension-associated increases in renal norepinephrine and dopamine, together with diabetes-associated compromised anti-oxidant systems contribute to increased renal oxidative stress in diabetes and hypertension. Elevations in renal cortical catecholamines and reactive oxygen species have important therapeutic implications for hypertensive diabetic patients.