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Angiotensin II receptors and functional correlates
P B Timmermans1, P Benfield, A T Chiu
1Du Pont Merck Pharmaceutical Company, Wilmington, DE 19880-0400.
American Journal of Hypertension
|December 1, 1992
Summary
Angiotensin II (ANG II) receptor antagonists like losartan redefine understanding of cardiovascular homeostasis. Research shows AT1-selective blockers mediate major ANG II effects, while AT2 receptor functions remain under investigation.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Molecular Biology
Background:
- Angiotensin II (ANG II) is central to the renin-angiotensin system, regulating cardiovascular homeostasis.
- The discovery of specific ANG II receptor antagonists, losartan (AT1-selective) and PD123177 (AT2-selective), has advanced understanding of receptor heterogeneity.
Purpose of the Study:
- To explore the functional roles and heterogeneity of Angiotensin II receptors.
- To investigate the mechanisms and therapeutic potential of ANG II receptor antagonists.
Main Methods:
- Utilized specific nonpeptide ANG II-receptor antagonists (losartan, PD123177) to probe receptor function.
- Cloning and sequencing of rat (AT1A, AT1B) and human ANG II receptors.
- Identification of atypical angiotensin-binding sites.
Main Results:
- Losartan-sensitive sites mediate key ANG II effects: vasoconstriction, hormone release, and drinking behavior.
- AT2 receptor functions are less understood but may involve ion channel modulation and collagen metabolism.
- Human and rat AT1 receptors have been cloned, with human receptors showing high affinity for losartan.
Conclusions:
- ANG II receptor heterogeneity is widespread across tissues and species.
- AT1-selective antagonists like losartan represent a new therapeutic class for cardiovascular conditions.
- Further research into AT2 receptor functions and atypical binding sites is warranted.