Renin-angiotensin system enzyme inhibitors

E. H. Ulm, W. J. Greenlee, Inhibitors of the Renin-Angiotensin System Enzymes , in Design of Enzyme Inhibitors as Drugs , Eds. M. Sandler, H. J. Smith, Oxford University Press, Oxford, 1989, p. 146- 177. 

The angiotensin I-converting enzyme (ACE) participates in regulating blood pressure in the renin-angiotensin system. The inhibitors such as captopril (Suetsuna and Chen, 2001) and enalapril (Sawayama et ah, 1990) have been used as antih)/pertensive drugs. The ACE-inhibitory activity of various source have studied, and it was found that some ACE-inhibitory peptides were produced by enzymatic digestion of various marine food proteins, including tuna muscle (Kohama et al., 1991 Qndetti, 1977), sardine muscle (Suetsima et al., 1991), dried bonito (Yokoyama et ah, 1992), dried-salted fish (Astawan et ah, 1995), fish sauce (Okamoto et al, 1995), and fish water-soluble protein (Wako et ah, 1999). 

The struggle to obtain the crystal stmcture of angiotensinanother example. ACE converts inactive angiotensin I to active angiotensin II which plays a critical role in the renin-angiotensin system. The many ACE inhibitors in clinical use were developed without knowledge of the ACE structure. 

The peptides are normally formed from a precursor molecule - angiotensinogen - an a2-globulin in the blood, by the action of a 340 amino acid glycoprotein called renin, which acts as an aspartyl protease enzyme (see renin inhibitors). Renin, and its precursor protein, are both stored in the juxtaglomerular cells of the kidney, and release is controlled by three different pathways within the kidney sensitive to Na -transport, blood vessel stretch and Pi-adrenoceptor activation, respectively. Overall, activation of the renin-angiotensin systems is hypertensive, but serves to increase renal perfusion. 

Inhibitors of the Renin-Angiotensin System - This area was reviewed in detail in the previous Annual Reports. Other useful reviews on the renin-angiotensin system (RAS), > factors Influencing renin release, the rationale and SARs for angiotensin converting enzyme (CE) inhibitors, and animal pharmacology of captopril have appeared. Of major interest during the past year has been the first reports of chronic treatment of hypertensive patients with the orally active CE inhibitor, captopril... 

Ondetti, M. A., Cushman, D. W. Enzymes of the renin-angiotensin system and their inhibitors. Annu. Rev. Biochem. 1982, 51, 283-308. 

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