Inhibitors also reduce plasma norepinephrine levels, and its resulting vasoconstriction effects, in heart failure patients, thus breaking the vicious circles of sympathetic and renin angiotensin system activation, which sustains the downward spiral in cardiac function in congestive heart failure The ACE inhibitor enalapril has also been shown to reduce cardiac cachexia in patients with chronic heart failure. Cachexia is a poor prognostic sign in patients with chronic heart failure. ACE inhibitors are under early investigation for the treatment of frailty and muscle wasting (sarcopenia) in elderly patients without heart failure. Examples Currently, there are 10 ACE inhibitors approved for use in the United States by the FDA: captopril (1981), enalapril (1985), lisinopril (1987), benazepril (1991), fosinopril (1991), quinapril (1991), ramipril (1991), perindopril (1993), moexipril (1995) and trandolapril (1996). ACE inhibitors are easily identifiable by their common suffix, '-pril'. ACE inhibitors can be divided into three groups based on their molecular structure of the enzyme binding sites (sulfhydryl, phosphinyl, carboxyl) to the active center of ACE: Sulfhydryl-containing agents Alacepril Captopril (trade name Capoten), the first ACE inhibitor. Zofenopril These agents appear to show antioxidative properties but may be involved in adverse events such as skin eruptions. Dicarboxylate-containing agents This is the largest group, including: Enalapril (Vasotec/Renitec/Berlipril/Enap/Enalapril Profarma) Ramipril (Altace/Prilace/Ramace/Ramiwin/Triatec/Tritace/Ramitac) Quinapril (Accupril) Perindopril (Coversyl/Aceon/Perindo) Lisinopril (Listril/Lopril/Novatec/Prinivil/Zestril, Lisidigal) Benazepril (Lotensin) Imidapril (Tanatril) Trandolapril (Mavik/Odrik/Gopten) Cilazapril (Inhibace) Phosphonate-containing agents Fosinopril (Fositen/Monopril) is the only member of this group Naturally occurring A comprehensive resource on anti-hypertensive peptides is available in form of a database. It contains around 1700 unique antihypertensive peptides Arfalasin (HOE 409) is angiotensin antagonist. Dairy products Casokinins and lactokinins, breakdown products of casein and whey, occur naturally after ingestion of milk products, especially cultured milk. Their role in blood pressure control is uncertain. The lactotripeptides Val-Pro-Pro and Ile-Pro-Pro produced by the probiotic Lactobacillus helveticus or derived from casein have been shown to have ACE-inhibiting and antihypertensive functions. In one study, L. helveticus PR4 was isolated from Italian cheeses. Comparative information All ACE inhibitors have similar antihypertensive efficacy when equivalent doses are administered. The main differences lie with captopril, the first ACE inhibitor. Captopril has a shorter duration of action and an increased incidence of adverse effects. It is also the only ACE inhibitor capable of passing through the blood–brain barrier, although the significance of this characteristic has not been shown to have any positive clinical effects. In a large clinical study, one