Angiotensin‐Converting Enzyme Inhibition and Angiotensin AT1 Receptor Blockade Downregulate Angiotensin‐Converting Enzyme Expression and Attenuate Renal Injury in Streptozotocin‐Induced Diabetic Rats

Abstract

Angiotensin-converting enzyme (ACE) is upregulated in the diabetic kidney and contributes to renal injury. This study investigates the possible beneficial effects of the ACE inhibitor (ACEI), enalapril and the AT1 receptor blocker (ARB), valsartan, on renal ACE expression, renal structure, and function in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were allocated into four groups: control, STZ-diabetic rats, and STZ-diabetic rats treated with either enalapril (10 mg/kg/day) or valsartan (50 mg/kg/day) for 8 weeks. Enalapril and valsartan reduced renal ACE mRNA and protein expression, Na(+) /K(+) -ATPase activity, oxidative stress, and serum transforming growth factor-β1 levels compared to the diabetic group. Both treatments normalized renal nitrate/nitrite levels and ameliorated the observed histopathological changes. In conclusion, ACE downregulation by ACEI and ARB indicates that angiotensin II upregulates ACE through AT1 receptor. Prevention of diabetes-induced changes in ACE expression and Na(+) /K(+) -ATPase activity could be a new explanation of the renoprotective effects of ACEIs and ARBs.

Effects of Dangguibuxue decoction on rat glomerular mesangial cells cultured under high glucose conditions

“…Thus, the inhibitory action of DBD on α-SMA suggests its potential anti-fibrotic effect that may protect against diabetic nephropathy. HYP is a specific amino acid of collagen; and widely used as a marker for collagen production [36]. We also detected reduced HYP secretion in DBD-treated GMCs, which further supports the anti-fibrotic effect of DBD in diabetic nephropathy.…”

The effects of anti‐hypertensives and type 2 diabetes on salivary flow and total antioxidant capacity

“…ACE inhibitors had been shown to attenuate the progression of cardiac and renal impairments related to diabetes by different mechanisms: suppression of ACE upregulation, improvement of endothelial function, and protective antioxidant action (O'Driscoll et al , ; de Cavanagh et al , ; Motawi et al , ). Our results showed that in the presence of enalapril salivary TAC, as an indicator of overall antioxidant protection, in hypertensive patients with and without DM type 2 was similar to that in healthy subjects while in the presence of metoprolol was reduced in hypertensive patients with and without DM type 2.…”

Ruboxistaurin attenuates diabetic nephropathy via modulation of TGF-β1/Smad and GRAP pathways

“…Renal pathophysiology is elicited by activation of angiotensin II type 1 (AT1) receptors at all stages of renovascular disease. It has been reported that hyperglycaemia directly activate mesangial and proximal tubular cells renin angiotensin system which is responsible for the production of angiotensin II that activate the AT1 receptor . Activation of AT1 receptor results in haemodynamic and trophic effects leading to glomerular hypertension, hyperfiltration and increased production of TGF‐β1 that contribute to the pathogenesis of renal damage .…”

“…Activation of AT1 receptor results in haemodynamic and trophic effects leading to glomerular hypertension, hyperfiltration and increased production of TGF‐β1 that contribute to the pathogenesis of renal damage . For many years, AT1‐receptor blockers have been widely used for slowing down or preventing renal damage in diabetes . It is reported that the renoprotective effect of valsartan as AT1 antagonist is associated with improved renal function, reduced albuminuria, decline in glomerular filtration rate and glomerulosclerotic index in addition to decreased expression of TGF‐β1 .…”