Kininase angiotensin converting enzyme

Figure 17.5 The dual vasodilatoiy effect of inhibitors of the angiotensin-converting enzyme (ACE). The ACE inhibitors not only inhibit ACE but also the kininase which degrades bradykinin. (See also Chapter 22).

Figure 7. Inhibition of the angiotensin converting enzyme, or kininase II.

ACE inhibitors (ACEIs) (e.g., captopril) inhibit kininase II (angiotensin-converting enzyme), blocking the formation of angiotensin II and preventing its activation of AT-1 receptors in the adrenal cortex —> 4, aldosterone and its effect on vasculature, thereby i vasoconstriction. ACEIs also inhibit the metabolism of bradykinin (BK), which causes NO/EDRF-mediated vasodilation - l TPR. 

I l urc 4. Kmm generation and degradation cascade and points of inhibitions by various inhibitors. AC lil, angiotensin converting enzyme inhibitor. Captopril and enalapril inhibit Kininase II (ACE). CPNI, carboxypeptidase N inhibitor. Dotted lines show possible... 

AIIRAs do not inhibit ACE (kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin), nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. Pharmacokinetics ... 

Costerousse O, Jaspard E, Wei L, Corvol P. Alhenc-Gelas F. The angiotensin I-converting enzyme (kininase II) Molecular organization and regulation of its expression in humans. J Cardiovasc Pharmacol 1992 20(Suppl. 9) S10-S15. 

The angiotensin I-converting enzyme (ACE), designated peptidyl-dipeptidase A (E.C.3.4.15.1), is identical to the bradykinin-metabolizing enzyme kininase II (38). Its early history and initial characterizations have been reviewed (51-54). It was discovered by Skeggs and co-workers (55), and in their pioneering work they showed it to be inhibited by ethylene-diaminetetraacetic acid (EDTA) (37), to remove a dipeptide from the carboxyl terminus of angiotensin I (then called hypertensin I [56]) and to be activated by sodium chloride (55). The fact that ACE is a Zn2+-contain-ing peptidase was first reported by Das and Sofler in 1975 (57). 

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