What question did this study set out to answer?

To characterize the binding profile of the AT1-selective antagonist BIBR 277 in rat kidneys and evaluate its effects on renal hemodynamics and function both in vitro and in vivo.

February 1, 1994Journal of Hypertension

Effects on Binding Characteristics and Renal Function of the Novel, Non-Peptide Angiotensin Ii Antagonist Bibr 277 in the Rat

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Why the study?

Does the novel angiotensin II antagonist BIBR277 alter renal function and binding characteristics in rat models?

Population

Rat kidney cortical membrane preparations, isolated constant-pressure perfused rat kidneys, and…

Comparison

BIBR277 vs Vehicle-treated control group

Design

Preclinical

Authors

WWWolfgang WienenBoehringer Ingelheim (Germany)MEMichael EntzerothMerck (Singapore)

Discussion

Member takes

Implication

Should not yet change practice; hypothesis-generating for AT1 antagonism effects on human renal function.

Key Points

To characterize the binding profile of the AT1-selective antagonist BIBR 277 in rat kidneys and evaluate its effects on renal hemodynamics and function both in vitro and in vivo.
Assessed receptor binding characteristics using [125I]-Ang II displacement and autoradiography in rat renal cortex, glomeruli, and medulla.
Evaluated in vitro renal hemodynamics and function using isolated, constant-pressure perfused rat kidneys exposed to BIBR 277 alone or alongside indomethacin and frusemide.
Measured in vivo blood pressure, heart rate, urinary flow, and electrolyte excretion following intravenous administration of BIBR 277 (0.1, 0.3, and 1 mg/kg) in anesthetized rats.
BIBR 277 selectively bound to AT1 receptors, completely inhibiting specific [125I]-(Sar1,Ile8)-Ang II binding in renal tissue at 1 µmol/l.
In isolated kidneys, BIBR 277 dose-dependently increased perfusate flow, urinary flow, and glomerular filtration rate up to 115%, 130%, and 112% of baseline, respectively, and amplified frusemide-induced diuresis from 140% to up to 200%.
In vivo, BIBR 277 significantly lowered blood pressure at 0.3 and 1 mg/kg, while the 0.3 mg/kg dose elicited a 2.0-fold increase in urinary flow and a 2.47-fold increase in sodium excretion without altering potassium excretion.

Structured PICO

Does the novel angiotensin II antagonist BIBR277 alter renal function and binding characteristics in rat models?

Population

Rat kidney cortical membrane preparations, isolated constant-pressure perfused rat kidneys, and anaesthetized rats

Intervention

BIBR277 (in vitro: 0.01, 0.1, and 1 mumol/l; in vivo: 0.1, 0.3, and 1 mg/kg intravenously)

Comparator

Vehicle-treated control group

Outcome

Binding characteristics to Ang II receptors and renal function (perfusate flow, urinary flow, glomerular filtration rate, sodium and potassium excretion)surrogate

BIBR277 is a potent AT1 receptor antagonist that demonstrates significant diuretic and natriuretic effects in rat models.

Cite This Study

Wienen et al. (1994) studied this question.

synapsesocial.com/papers/6a7ab9dc02ab7a73dd031009 https://doi.org/10.1097/00004872-199402000-00003

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Effects on Binding Characteristics and Renal Function of the Novel, Non-Peptide Angiotensin Ii Antagonist Bibr 277 in the Rat

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Effects on Binding Characteristics and Renal Function of the Novel, Non-Peptide Angiotensin Ii Antagonist Bibr 277 in the Rat

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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