Renal GLUT1 reduction depends on angiotensin-converting enzyme inhibition in diabetic hypertensive rats.

Angiotensin-converting enzyme (ACE) inhibitors are used in diabetic kidney disease to reduce systemic/intra-glomerular pressure. The objective of this study was to investigate whether reducing blood pressure (BP) could modulate renal glucose transporter expression, and urinary markers of diabetic nephropathy in diabetic hypertensive rats treated with ramipril or amlodipine. Diabetes was induced in spontaneously-hypertensive rats (~210 g) by streptozotocin (50mg/kg). Thirty days later, animals received ramipril 15 μg/kg/day (R, n=10), or amlodipine 10mg/kg/day (A, n=8,) or water (C, n=10) by gavage. After 30-day treatment, body weight, glycaemia, urinary albumin and TGF-β1 (enzyme-linked immunosorbent assay) and BP (tail-cuff pressure method) were evaluated. Kidneys were removed for evaluation of renal cortex glucose transporters (Western blotting) and renal tissue ACE activity (fluorometric assay). After treatments, body weight (p=0.77) and glycaemia (p=0.22) were similar among the groups. Systolic BP was similarly reduced (p<0.001) in A and R vs. C (172.4 ± 3.2; 1867 ± 3.7 and 202.2 ± 4.3 mmHg; respectively). ACE activity (C: 0.903 ± 0.086; A: 0.654 ± 0.025, and R: 0.389 ± 0.057 mU/mg), albuminuria (C: 264.8 ± 15.4; A: 140.8 ± 13.5 and R: 102.8 ± 6.7 mg/24h), and renal cortex GLUT1 content (C: 46.81 ± 4.54; A: 40.30 ± 5.39 and R: 26.89 ± 0.79 AU) decreased only in R (p<0.001, p<0.05 and p<0.001; respectively). We concluded that the blockade of the renin-angiotensin system with ramipril reduced early markers of diabetic nephropathy, a phenomenon that cannot be specifically related to decreased BP levels.

da Silva AS ，Dias LD ，Borges JF ，Markoski MM ，de Souza MS ，Irigoyen MC ，Machado UF ，Schaan BD ... -  《-》

Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats.

Souza MS ，Machado UF ，Okamoto M ，Bertoluci MC ，Ponpermeyer C ，Leguisamo N ，Azambuja F ，Irigoyen MC ，Schaan BD ... -  《-》

Impact of renal denervation on renal content of GLUT1, albuminuria and urinary TGF-beta1 in streptozotocin-induced diabetic rats.

D'Agord Schaan B ，Lacchini S ，Bertoluci MC ，Irigoyen MC ，Machado UF ，Schmid H ... -  《AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL》

Preservation of kidney function with combined inhibition of NADPH oxidase and angiotensin-converting enzyme in diabetic nephropathy.

Antihypertensive therapies such as angiotensin-converting enzyme-1 inhibitors (ACEi) slow the decline in renal function seen with diabetic nephropathy, although there is still progression ultimately to end-stage renal disease. The aim of this study was to determine if there were added renoprotective benefits seen by combining ACEi with blockade of NADPH oxidase. Sprague-Dawley diabetic and non-diabetic rats were randomized to receive intervention therapy with apocynin (15 mg/kg/day, weeks 16-32), apocynin + the ACEi ramipril (1 mg/kg/day, weeks 16-32), or ramipril alone (1 mg/kg). All three treatments retarded the development of albuminuria in the diabetic rats. Apocynin conferred its benefit either as a monotherapy or in combination with ramipril without affecting blood pressure per se. Renal morphological injury was attenuated by all three treatment strategies. Diabetes was associated with increasing renal fibronectin and type IV collagen protein expression, with the combination regimen resulting in the highest decrease in extracellular matrix accumulation. All three treatments prevented the diabetes-associated increases in renal cytosolic superoxide generation as well as urinary isoprostanes. While renal TGF-beta1 activation was reduced by ramipril treatment but not by apocynin as a monotherapy, kidney cortical membranous VEGF was reduced by apocynin as monotherapy and dual therapy but not by ramipril alone. Combination of NADPH oxidase blockade with ACE inhibitors is a promising regimen which warrants further investigation as a way to confer additional renoprotection in diabetes.

Thallas-Bonke V ，Coughlan MT ，Bach LA ，Cooper ME ，Forbes JM ... -  《-》

Comparative antihypertensive and renoprotective effects of telmisartan and lisinopril after long-term treatment in hypertensive diabetic rats.

Wienen W ，Richard S ，Champeroux P ，Audeval-Gerard C ... -  《JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM》