angiotensin receptor (ARBs), or at the receptor for aldosterone, which is under control of both the renin-angiotensin system and other systemic and local influences (aldosterone antagonists).
Angiotensin converting enzyme inhibitors are the best studied class of agents in HF, with multiple mechanisms of benefit for both HF, coronary disease, and other atherosclerotic vascular disease, as well as diabetic nephropathy.
During chronic therapy with ACEIs, the renin-angiotensin system demonstrates partial “escape” from inhibition with “normalization” of angiotensin levels, in part owing to alternative local pathways for production of angiotensin. This leaves the potential for benefit from additional therapy with ARBs and with the aldosterone antagonists.
ACE INHIBITORS (ACEIs)
Angiotensin converting-enzyme inhibitors interfere with the renin-angiotensin system by inhibiting the enzyme responsible for the conversion of angiotensin I to angiotensin II, but it is not clear whether the effects of ACE inhibitors can be explained solely by the suppression of angiotensin II.
ACE inhibition not only interferes with the renin-angiotensin system but also enhances the action of kinins and augments kinin-mediated prostaglandin, and kinin potentiation may play an important role in mediating the effects of ACE inhibitors. This seems to be suggested by both experimental and clinical studies. In experimental models of HF, ACE inhibitors modify cardiac remodeling more favorably than angiotensin II receptor antagonists35, and this advantage of ACE inhibitors is abolished by concurrent administration of kinin antagonists36.
Furthermore, in the clinical setting, ACE inhibitors produce long-term benefits even though circulating levels of angiotensin II are not suppressed during prolonged treatment37, and these benefits may be attenuated by the co-administration of aspirin38, which can block kinin-mediated prostaglandin synthesis.
Effect of ace inhibitors in the management of HF
35 Bastien NR, Juneau AV, Ouellette J, Lambert C. Chronic AT1 receptor blockade and angiotensin- converting enzyme (ACE) inhibition in (CHF 146) cardiomyopathic hamsters: effects on cardiac hypertrophy and survival. Cardiovasc Res 1999;43:77-85.
36 Linz W, Scholkens BA. A specific B2-bradykinin receptor antagonist HOE 140 abolishes the antihypertrophic effect of ramipril. Br J Pharmacol 1992;105:771-2.
37 Juillerat L, Nussberger J, Menard J, et al. Determinants of angiotensin II generation during converting enzyme inhibition. Hypertension 1990;16:564-72.
38 Al Khadra AS, Salem DN, Rand WM, Udelson JE, Smith JJ,Konstam MA. Antiplatelet agents and survival: a cohort analysis from the Studies of Left Ventricular Dysfunction (SOLVD) trial. J Am Coll Cardiol 1998;31:419-25.