Angiotensin-Converting Enzyme Inhibitors

Abstract

Abstract-ACE inhibitors have achieved widespread usage in the treatment of cardiovascular and renal disease. ACE inhibitors alter the balance between the vasoconstrictive, salt-retentive, and hypertrophic properties of angiotensin II (Ang II) and the vasodilatory and natriuretic properties of bradykinin and alter the metabolism of a number of other vasoactive substances. ACE inhibitors differ in the chemical structure of their active moieties, in potency, in bioavailability, in plasma half-life, in route of elimination, in their distribution and affinity for tissue-bound ACE, and in whether they are administered as prodrugs. Thus, the side effects of ACE inhibitors can be divided into those that are class specific and those that relate to specific agents. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have proved effective in the treatment of hypertension, they decrease mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction, and they delay the progression of diabetic nephropathy. Ongoing studies will elucidate the effect of ACE inhibitors on cardiovascular mortality in essential hypertension, the role of ACE inhibitors in patients without ventricular dysfunction after myocardial infarction, and the role of ACE inhibitors compared with newly available angiotensin AT 1 receptor antagonists. MechanismACE, or kininase II, is a bivalent dipeptidyl carboxyl metallopeptidase present as a membrane-bound form in endothelial cells, in epithelial or neuroepithelial cells, and in the brain and as a soluble form in blood and numerous body fluids. 1 ACE, or kininase II, cleaves the C-terminal dipeptide from Ang I and bradykinin and a number of other small peptides that lack a penultimate proline residue. Thus, ACE is strategically poised to regulate the balance between the RAS and the kallikrein-kinin system.The RAS plays a pivotal role in blood pressure regulation (Fig 1). Reduced sodium delivery at the macula densa, decreased renal perfusion pressure, and sympathetic activation all stimulate secretion of renin by the juxtaglomerular cell, the classic source of renin in the circulating RAS.

Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm

“…This compensatory mechanism causes potent vasoconstriction (with an increase in total peripheral resistance and therefore afterload) and salt and water retention to increase circulatory volume (Furberg and Yusuf, 1985). ACE is a common link between the RAAS and kallikrein–kinin pathways, converting angiotensin I to the salt‐retentive, vasoconstrictive and hypertrophic angiotensin II, and degrading the vasodilatory and salt‐wasting bradykinin (Brown and Vaughan, 1998). It is now recognized that RAAS activation incorporates a tissue component (particularly cardiac, vascular and renal) that is independent from the systemic endocrine effects (Dzau and Re, 1994).…”

Chronic pretreatment of ACEI reduces no‐reflow in patients with acute myocardial infarction treated with primary angioplasty

“…In addition, ACEI limits the vasoconstriction by blocking the conversion of angiotensin I to angiotensin II and preventing the degradation of bradykinin into inactive peptides. 11 ACEI has also favorable effects on platelet activity, 12 thrombosis 13 and plaque stability. 14 These pleiotropic effects could also contribute to the preservation of microvascular function during ischemia and reperfusion.…”

Modulating atherosclerosis through inhibition or blockade of angiotensin

“…29,30 Angiotensin II is cleaved from angiotensin I by the action of the ACE. 30 Another important action of the ACE is to catalyze the degradation of bradykinin. Bradykinin permits vasodilation by stimulating production of endothelium-derived NO.…”

“…Bradykinin permits vasodilation by stimulating production of endothelium-derived NO. 30 Several atherogenic activities have been described for angiotensin II. It stimulates hypertrophic growth of vascular smooth muscle cells; 31 it induces synthesis of basic fibroblast growth factor, a potent mitogen for vascular smooth muscle cells; 32 and it has been shown to recruit monocytes into the vessel wall (a critical early step in the development of atherosclerosis) in a rabbit model of early accelerated atherosclerosis.…”