Sergio Henrique Ferreiri (b. 1934), John Vane (1927–2004)
Should one experience a sudden drop in blood pressure or a reduction in blood volume, such as might occur after dehydration or bleeding, a sequence of compensatory events seeks to restore homeostasis, the normal state of balance in the body. Angiotensin II (Ang II), a highly active peptide formed in the liver, counters such drops in blood pressure by altering the activity of blood vessels to increase blood pressure and by prompting the kidney to retain body salt and water. The enzyme responsible for the formation of Ang II from the inactive Ang I is angiotensin-converting enzyme (ACE), first identified in the 1950s.
FROM PIT VIPER VENOM TO ACE INHIBITOR. A decade later, the Brazilian pharmacologist Sergio Ferreiri extracted a component from the venom of Bothrops jararaca, a South American pit viper, and brought it to the London laboratory of John Vane. The extract and its active chemical teprotide inhibited ACE and provided a novel approach for the treatment of hypertension (high blood pressure). Scientists at the Squibb Institute for Medical Research in New Jersey further evaluated teprotide and found it inactive by mouth. However, the discovery led Squibb scientists to synthesize captopril (Capoten), the first orally active ACE inhibitor, which they marketed in 1981. Approximately ten similar drugs are now available.
The ACE inhibitors have proved very important, not only for the treatment of mild-to-severe hypertension in patients experiencing other problems, but also for managing a range of cardiovascular conditions. When used for heart failure, in which they are considered integral to treatment, ACE inhibitors increase the ability of patients to function and reduce mortality rates.
Multiple clinical studies have shown that ACE inhibitors reduce the death rate when administered at the time of a heart attack. In addition, diabetes is the leading cause of end-stage kidney disease. ACE inhibitors help to prevent or delay the progression in such patients.
SEE ALSO Digitalis (1775), Diuril (1958), Propranolol (1964), Lasix (1966).
This poster provides valuable advice for people with hypertension: Maintain a healthy body weight, eliminate salt from the diet, kick the cigarette habit, take blood-pressure medication regularly, and monitor blood pressure.