Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy.

Björck, S; Nyberg, Gudrun; Mulec, H.; Granérus, G.; Herlitz, Hans; Aurell, Mattias

doi:10.1136/bmj.293.6545.471

Cited by 405 publications

(107 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hypertension is often associated with diabetic nephropathy [2], and effective antihypertensive treatment has proven to be effective in slowing the progression rate of nephropathy [3][4][5]. Recent studies in patients with diabetic nephropathy suggest that the use of angiotensin converting enzyme (ACE) inhibitors may possess specific advantages in decreasing proteinuria and slowing progression of nephropathy [6][7][8][9]. Nevertheless, whether such renal effects can be seen only with ACE inhibitors or whether ACE inhibitors have more beneficial renal effects as compared to other conventional antihypertensive drugs is uncertain.…”

mentioning

confidence: 99%

Comparison of the renal effects of angiotensin converting enzyme inhibitor and calcium antagonist in hypertensive Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria: a randomised controlled trial

1989

View full text Add to dashboard Cite

Summary. Seven of eight hypertensive Type 2 (non-insulindependent) diabetic patients with microalbuminuria completed a randomised crossover trial to compare the renal effects of angiotensin converting enzyme inhibitor (enalapril) and calcium antagonist (nicardipine). Four-week fixed oral maintenance dosages of enalapril (10-20 rag/day) and nicardipine (60-120 rag/day) significantly (p<0.05) lowered the systolic and diastolic blood pressures without altering renal blood flow, glomerular filtration rate and filtration fraction. Both drugs significantly reduced (p< 0.05) urinary albumin excretion rate and fractional clearance of albumin to similar extents. Total renal vascular resistance decreased significantly by nicardipine (p<0.05) and non-significantly by enalapril. Plasma osmotic pressure, plasma aldosterone concentration, total serum protein concentration, serum electrolytes and HbAlc remained unchanged by these drugs, whereas plasma renin activity was significantly higher (/7<0.05) in the enalapril than in the control and nicardipine phases. These results suggest that both drugs have similar renal function preserving effects with a concomitant hypotensive action in hypertensive Type 2 diabetic patients with microalbuminuria, and that the angiotensin converting enzyme inhibitor may not have advantageous renal effects when compared to the calcium antagonist and vice versa. Both drugs might be useful for treatment of high blood pressure in hypertensive diabetic patients, if long-term studies of these drugs can be shown to benefit the patients over other conventional antihypertensive therapies.

show abstract

mentioning

confidence: 99%

Comparison of the renal effects of angiotensin converting enzyme inhibitor and calcium antagonist in hypertensive Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria: a randomised controlled trial

1989

View full text Add to dashboard Cite

show abstract

“…5,9 Several studies have linked increased renin angiotensin aldosterone system activity to enhanced renal Nox activity and ROS generation. 5,17 Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers slow progression of proteinuria in models of diabetes, and these effects may be, in part, independent of their effects on systemic BP, [17][18][19][20] because direct activation of Nox enzymes through the angiotensin II (AngII)/AT1 receptor (AT1R) pathway leads to oxidative stress. In vitro studies in both human and rodent cell lines have also shown that Nox family member expression and activity are regulated by disease-associated factors, including AngII, ET-1, TGF-b, high glucose, mechanical stretch, and PDGF (factors that are upregulated in the diabetic milieu).…”

mentioning

confidence: 99%

Nephropathy and Elevated BP in Mice with Podocyte-Specific NADPH Oxidase 5 Expression

Holterman¹,

Thibodeau²,

Towaij³

et al. 2014

Journal of the American Society of Nephrology

117

122

View full text Add to dashboard Cite

NADPH oxidase (Nox) enzymes are a significant source of reactive oxygen species, which contribute to glomerular podocyte dysfunction. Although studies have implicated Nox1, -2, and -4 in several glomerulopathies, including diabetic nephropathy, little is known regarding the role of Nox5 in this context. We examined Nox5 expression and regulation in kidney biopsies from diabetic patients, cultured human podocytes, and a novel mouse model. Nox5 expression increased in human diabetic glomeruli compared with nondiabetic glomeruli. Stimulation with angiotensin II upregulated Nox5 expression in human podocyte cultures and increased reactive oxygen species generation. siRNA-mediated Nox5 knockdown inhibited angiotensin II-stimulated production of reactive oxygen species and altered podocyte cytoskeletal dynamics, resulting in an Rac-mediated motile phenotype. Because the Nox5 gene is absent in rodents, we generated transgenic mice expressing human Nox5 in a podocyte-specific manner (Nox5 pod+ ). Nox5 pod+ mice exhibited early onset albuminuria, podocyte foot process effacement, and elevated systolic BP. Subjecting Nox5 pod+ mice to streptozotocin-induced diabetes further exacerbated these changes. Our data show that renal Nox5 is upregulated in human diabetic nephropathy and may alter filtration barrier function and systolic BP through the production of reactive oxygen species. These findings provide the first evidence that podocyte Nox5 has an important role in impaired renal function and hypertension. Albuminuria is a clinical marker of kidney dysfunction that arises in most glomerulopathies and is associated with poor prognoses for ESRD, hypertension, and cardiovascular mortality. Changes to the podocyte (e.g., foot process effacement, hypertrophy, detachment, and loss) underlie the development and progression of albuminuria and thereby highlight the critical role for these cells in upholding the glomerular filtration barrier. 1,2 Therefore, identifying factors that induce podocyte injury and loss is essential to understanding the mechanisms of filtration barrier dysfunction. Of the many factors implicated in podocyte dysfunction, excessive production of reactive oxygen species (ROS; oxidative stress) may be particularly important. [3][4][5][6] Although sources of ROS are numerous, the NADPH oxidase (Nox) family of enzymes yields significant superoxide production in the

show abstract

“…Inhibitors of angiotensin-con-verting enzyme (ACE) and angiotensin II receptor blockers are thought to be involved in the development of DN (Bjorck et al 1986;Whitty and Jackson 1988;Onozato et al 2002). We previously reported the frequent occurrence of nephropathy in diabetic patients with genotype D of the ACE gene (Mizuiri et al 1995(Mizuiri et al , 1997 and that, in the kidney from the D genotype population, the number of transcripts of the ACE gene is higher than in I genotype (Mizuiri et al 2001), suggesting that ACE activity contributes to the development of DN.…”

mentioning

confidence: 99%

Nuclear Factor-.KAPPA.B Activation in Diabetic Rat Kidney: Evidence for Involvement of P-Selectin in Diabetic Nephropathy

Iwamoto

Mizuiri

Arita

et al. 2005

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Activation of a transcription factor, nuclear factor-κ B (NF-κ B), is a key step in the pathogenesis of diabetic nephropathy. In this study, we investigated the role of P-selectin, a platelet-derived adhesion molecule, in diabetic nephropathy by examining the activation status of NF-κ B in the renal cortex of streptozotocin (STZ)-treated rats. The STZ treatment induced pathogenetic parameters such as increased creatinine clearance, increased blood glucose and massive albuminuria in a timedependent manner. Electrophoretic mobility shift assays (EMSAs) with a specific probe, representing the P-selectin gene promoter, revealed the activation status of NF-κ B in the STZ-treated rats, as judged by the time-dependent increase in the formation of the specific protein-DNA complexes. This increase was associated with the increased pathogenetic parameters. Supershift assays with specific antibodies revealed that p50, but not p52, p65, Rel B, or c-Rel, may be involved in the activation of NF-κ B, though the component primarily responsible for the increase could not be determined. Western blot analysis confirmed an increase in P-selectin in STZ-treated rats. Notably, treatment with ammonium pyrrolidinedithiocarbamate, an antioxidant and inhibitor of NF-κ B, inhibited the activation of NF-κ B in STZ-treated rats and decreased P-selectin in the renal cortical tissue. Our results indicate that expression of the P-selectin gene is induced through the activation of NF-κ B and that P-selectin may be involved in the pathogenesis of diabetic nephropathy. nuclear factor-κ B; P-selectin; diabetic nephropathy; rat; streptozotocin

show abstract

Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy.

Cited by 405 publications

References 12 publications

Comparison of the renal effects of angiotensin converting enzyme inhibitor and calcium antagonist in hypertensive Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria: a randomised controlled trial

Comparison of the renal effects of angiotensin converting enzyme inhibitor and calcium antagonist in hypertensive Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria: a randomised controlled trial

Nephropathy and Elevated BP in Mice with Podocyte-Specific NADPH Oxidase 5 Expression

Nuclear Factor-.KAPPA.B Activation in Diabetic Rat Kidney: Evidence for Involvement of P-Selectin in Diabetic Nephropathy

Contact Info

Product

Resources

About