What question did this study set out to answer?

To evaluate the relative contributions of angiotensin II suppression and bradykinin accumulation in mediating the structural and functional renoprotective effects of ACE inhibition in diabetic nephropathy.

October 1, 1997Diabetes

Role of Angiotensin II and Bradykinin in Experimental Diabetic Nephropathy: Functional and Structural Studies

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Why the study?

Does angiotensin II blockade or bradykinin-B2 receptor antagonism mediate the renoprotective effects of ACE inhibitors in experimental diabetic nephropathy?

Population

Male Sprague-Dawley diabetic and control rats

Comparison

Ramipril, valsartan, icatibant/HOE 140, and a… vs Untreated diabetic rats and non-diabetic control…

Design

Preclinical

Follow-up

24 weeks

Authors

TATerri J. AllenMerck & Co., Inc., Rahway, NJ, USA (United States)ZCZemin CaoBaker Heart and Diabetes Institute SYSherif YoussefMemorial University of Newfoundland

Discussion

Member takes

Implication

Angiotensin II blockade mediates ACE inhibitor renoprotection in diabetic rats; extends mechanistic data but leaves human translation open.

Key Points

To evaluate the relative contributions of angiotensin II suppression and bradykinin accumulation in mediating the structural and functional renoprotective effects of ACE inhibition in diabetic nephropathy.
Evaluated male Sprague-Dawley diabetic and control rats over a 24-week follow-up period.
Assigned diabetic rats to treatment with ramipril (ACE inhibitor), valsartan (AT1 blocker), HOE 140/icatibant (bradykinin-B2 antagonist), or combined ramipril and icatibant.
Measured monthly urinary albumin excretion, blood pressure, and glycated hemoglobin, followed by 6-month post-mortem assessment of kidney weight and glomerular ultrastructure.
Both equihypotensive ramipril and valsartan fully prevented the continuous progressive increase in urinary albumin excretion seen in untreated diabetic rats.
Both ACE inhibition and AT1 receptor blockade attenuated diabetes-induced increases in glomerular basement membrane thickness, glomerular volume, and total mesangial volume to an equivalent extent.
Icatibant produced no therapeutic effect on its own and did not attenuate the antialbuminuric or structural protective effects of ramipril.

Structured PICO

Does angiotensin II blockade or bradykinin-B2 receptor antagonism mediate the renoprotective effects of ACE inhibitors in experimental diabetic nephropathy?

Population

Male Sprague-Dawley diabetic and control rats

Intervention

Ramipril (ACE inhibitor), valsartan (angiotensin II-AT1 receptor antagonist), icatibant/HOE 140 (bradykinin-B2 receptor antagonist), and a combination of ramipril and icatibant

Comparator

Untreated diabetic rats and non-diabetic control rats

Outcome

Urinary albumin excretion, blood pressure, glycated hemoglobin, kidney weight, and glomerular ultrastructure (glomerular basement membrane thickness, glomerular volume, and total mesangial volume)surrogate

The renoprotective effects of ACE inhibitors in experimental diabetic nephropathy are primarily mediated by the blockade of angiotensin II rather than the prevention of bradykinin degradation.

Cite This Study

Allen et al. (1997) studied this question.

synapsesocial.com/papers/6a86c549713eb98b40ca09ce https://doi.org/10.2337/diacare.46.10.1612

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Implication

Angiotensin II blockade mediates ACE inhibitor renoprotection in diabetic rats; extends mechanistic data but leaves human translation open.

Role of Angiotensin II and Bradykinin in Experimental Diabetic Nephropathy: Functional and Structural Studies

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Role of Angiotensin II and Bradykinin in Experimental Diabetic Nephropathy: Functional and Structural Studies

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider