What question did this study set out to answer?

To determine whether unselective inhibition of endothelin receptors with PD 142,893 provides renoprotection in diabetic rats with established proteinuria, compared to the ACE inhibitor lisinopril.

March 1, 1998Diabetes

Unselective inhibition of endothelin receptors reduces renal dysfunction in experimental diabetes.

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Why the study?

Does PD 142,893 improve renal dysfunction in proteinuric streptozotocin diabetic rats?

Population

Streptozotocin diabetic rats that were already proteinuric

Comparison

Unselective ET/ET receptor antagonist, PD 142,893 vs ACE inhibitor and untreated control rats

Design

Preclinical

Authors

ABAriela BenigniMario Negri Institute for Pharmacological Research VCV ColosioMario Negri Institute for Pharmacological Research CBC BrenaMario Negri Institute for Pharmacological Research

Discussion

Member takes

Implication

Endothelin antagonism shows renoprotective potential in diabetic rat models; hypothesis-generating and should not yet change practice.

Key Points

To determine whether unselective inhibition of endothelin receptors with PD 142,893 provides renoprotection in diabetic rats with established proteinuria, compared to the ACE inhibitor lisinopril.
Administered the unselective endothelin receptor antagonist PD 142,893 or the ACE inhibitor lisinopril to streptozotocin-induced diabetic rats with preexisting proteinuria and to non-diabetic controls.
Measured mean systemic blood pressure, urinary protein and albumin excretion rates, and renal blood flow across treated and untreated groups.
Quantified renal endothelin-1 mRNA expression in isolated glomeruli and tubuli using Northern blot analysis and in situ hybridization.
PD 142,893 normalized systemic blood pressure, reduced urinary protein and albumin excretion, and improved renal blood flow in diabetic rats without affecting healthy controls.
Lisinopril exhibited renoprotective effects comparable to PD 142,893 while achieving greater systemic blood pressure reduction.
Both PD 142,893 and lisinopril substantially attenuated the marked upregulation of renal endothelin-1 gene expression found in diabetic glomeruli and tubules.

Structured PICO

Does PD 142,893 improve renal dysfunction in proteinuric streptozotocin diabetic rats?

Population

Streptozotocin diabetic rats that were already proteinuric

Intervention

Unselective ET(A)/ET(B) receptor antagonist, PD 142,893

Comparator

ACE inhibitor (lisinopril) and untreated control rats

Outcome

Systemic blood pressure, urinary protein and albumin excretion, and renal blood flowsurrogate

Unselective endothelin receptor antagonism with PD 142,893 provides renoprotection comparable to ACE inhibition in a rat model of diabetic nephropathy.

Cite This Study

Benigni et al. (1998) studied this question.

synapsesocial.com/papers/6a7e27ea412d7dea03256a85 https://doi.org/10.2337/diabetes.47.3.450

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Unselective inhibition of endothelin receptors reduces renal dysfunction in experimental diabetes.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Unselective inhibition of endothelin receptors reduces renal dysfunction in experimental diabetes.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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