Ace

Inactive Products Vasodilatation

Figure 18.3 • Bradykinin formation and action.

a nucleophilic attack of the amide carbonyl by the y-car-bonyl group of a glutamic acid residue to cause hydrolysis of the peptide. Figure 18.4 shows a hypothetical model of the hydrolysis of angiotensin I by the active site of ACE. ACE exists in more than one form. Somatic ACE that regulates blood pressure, found in most tissues, differs from the isoenzyme ACE found in the testis. Somatic ACE, in contrast to testicular ACE, contains two binding domains. The principal active site for hydrolysis is the domain located in the C-terminal half of somatic ACE.8

Because the renin-angiotensin system plays such an important role in regulating kidney function,9 aldosterone release,10 electrolyte balance, and blood volume, it is easy to recognize why targeting this pathway is beneficial in the management of high blood pressure and heart failure. Inhibitors of angiotensin-converting enzyme (ACE in hibitors) are often used to reduce the formation of the more potent angiotensin II. In addition, angiotensin receptor blockers (ARBs) can be used to prevent angiotensin II from acting on angiotensin receptors.11

Recently, there have been several agents investigated for their ability to inhibit renin, which in turn results in less angiotensin II being produced.12

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