Angiotensin biological actions

Ondetti, M.A. and Cushman, D.W. 1984. Angiotensin-converting enzyme inhibitors biochemical properties and biological actions. CRC Crit. Rev. Biochem. Mol. Biol. 16, 381-411. 

Petrillo, E.W. and Ondetti, M.A. 1982. Angiotensin-converting enzyme inhibitors, medical chemistry and biological actions. Med. Res. Rev. 2, 1-41. 

The biological action of a compound is also readily explicable if it mimics a natural substrate or mediator. This is the case for enzymes with inhibitors (angiotensin I and captopril), suicide substrates (GABA and vigabatrin). 

While the rate limiting step of the cascade is the renin release, the biological active component is the octapeptide angiotensin n. It is an essential regulator of fluid and electrolyte balance as well as blood pressure. It exerts its actions on various structures like blood vessels, adrenal cortex, kidney and central nervous system. Although at least two different receptor subtypes for angiotensin II have been identified (ATi and AT2) the ATi-subtype is responsible for most of the cardiovascular effects of the agonist. 

Although Ang I contains the peptide sequences necessary for all of the actions of the renin-angiotensin system, it has little or no biologic activity. Instead, it must be converted to Ang II by converting enzyme (Figure 17-1). Ang I may also be acted on by plasma or tissue... 

Although benzopiperazinones (l,2,3,4-tetrahydroquinoxalin-2-ones) are structurally related to benzodiazepines, their use in drug discovery is less well established. Examples of biological activity of benzopiperazinones include their action as inhibitors of aldose reductase [208], as partial agonists of the y-aminobutyric acid (GABA)/benzodiazepine receptor complex [209, 210], and as angiotensin II receptor antagonists [211]. In addition, derivatives with antiviral acti vity associated vfith HIV have been reported [212, 213]. 

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