What question did this study set out to answer?

To evaluate the pharmacological properties, receptor-binding affinities, and in vivo antihypertensive efficacy of a novel series of nonpeptide angiotensin II receptor antagonists, focusing on EXP9270 and DuP 753.

June 1, 1990HypertensionOpen Access

Nonpeptide angiotensin II receptor antagonists. Studies with EXP9270 and DuP 753.

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Population

Rat adrenal cortical microsomes, isolated rabbit aorta, high renin renal-hypertensive rats, guinea pig…

Design

Preclinical

Authors

PWPancras C. WongPreventive Cardiology WPWilliam A. PriceThe University of Texas Health Science Center at San Antonio ACAndrew T. ChiuHong Kong Polytechnic University

Discussion

Member takes

Implication

Validates integrated preclinical screening for Ang II antagonists; leaves open human translation and efficacy trials.

Key Points

To evaluate the pharmacological properties, receptor-binding affinities, and in vivo antihypertensive efficacy of a novel series of nonpeptide angiotensin II receptor antagonists, focusing on EXP9270 and DuP 753.
Evaluated binding inhibition of [3H]Ang II in rat adrenal cortical microsomes (IC50), functional antagonism in isolated rabbit aorta (pA2), and intravenous antihypertensive effects in renal-hypertensive rats (ED30).
Characterized oral potency and selectivity of EXP9270 and DuP 753 in rabbit aorta, guinea pig ileum, and conscious normotensive rats.
Binding affinity correlated significantly with functional antagonism and in vivo potency: IC50 vs. pA2 (r = -0.88), IC50 vs. intravenous ED30 (r = 0.79), and pA2 vs. intravenous ED30 (r = -0.93), with no agonistic activity observed.
DuP 753 and EXP9270 demonstrated oral antihypertensive activity with oral ED30 values of 0.59 mg/kg and 3.6 mg/kg, respectively.
DuP 753 selectively blocked the saralasin pressor response, Ang II-induced drinking behavior, and Ang II-induced aldosterone release in rats.

Structured PICO

Population

Rat adrenal cortical microsomes, isolated rabbit aorta, high renin renal-hypertensive rats, guinea pig ileum, and conscious normotensive rats

Intervention

Nonpeptide angiotensin II receptor antagonists (EXP9270 and DuP 753)

Outcome

Inhibitory effects on specific binding of [3H]Ang II, functional antagonism of contractile response to Ang II, and intravenous antihypertensive effects (IC50, pA2, and intravenous ED30)surrogate

Nonpeptide angiotensin II receptor antagonists EXP9270 and DuP 753 demonstrate specific, competitive Ang II receptor blockade and antihypertensive effects in preclinical models, establishing their potential as therapeutic agents.

Cite This Study

Wong et al. (1990) studied this question.

synapsesocial.com/papers/6a7a40b6bdf697b3de029084 https://doi.org/10.1161/01.hyp.15.6.823

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Nonpeptide angiotensin II receptor antagonists. Studies with EXP9270 and DuP 753.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Nonpeptide angiotensin II receptor antagonists. Studies with EXP9270 and DuP 753.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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