Angiotensin converting enzyme inhibitors (ACEI) represent the first class of antihypertensive agents that was designed and developed on the basis of a well-defined physiopathological axis of arterial hypertension, a vascular dis order that is now becoming one of the major causes of morbidity/mortality, not only in developed societies but also in the highly populated developing coun tries . CAPTOPRIL, the prototype of the "PRIL" family, which now comprises more than 40 molecule-species, was quite hazardous and the clinical develop ment almost failed when serious side-effects were reported in an alarmist fash ion in reputable scientific journals, such as the New England Journal of Medicine and Lancet. Squibb & Sons came very close to withdrawing CAPTOPRIL from clinical investigation . However, after re-examination of the data obtained from different categories of patients and appropriate dose-adjustments, the clinical use of CAPTOPRIL turned out to be revolutionary. The prototype, as well as other members of the "PRIL" family became the starting point for numerous basic and clinical research programs, focusing on the interactions of ACEI with the kinin, endothelin, and nitric oxide systems, and the contribution of the receptors for AT I, AT 2, bradykinin Bland B , ETA and ET B to the pharmacological actions 2 of the respective peptides. This research activity led to the development of new pharmacological agents, such as the angiotensin receptor antagonists and, more recently, the neutral endopeptidase inhibitors. In the near future, bradykinin receptor antagonists also will be available to modulate ACEI phar macological actions.
Comentarios de la gente - Escribir un comentario
No encontramos ningún comentario en los lugares habituales.
Otras ediciones - Ver todas
ACE inhibitors ACEI angiotensin II type angiotensin-converting enzyme angiotensin-II angiotensinogen antihypertensive aorta aortic arterial wall arterioles associated AT1 receptor B2 kinin receptor baroreflex Benetos blockade blood flow blood pressure bradykinin capillary captopril cardiac Cardiol Cardiovasc Pharmacol cardiovascular carotid artery chronic Circ Res Circulation clinical compliance congestive heart failure converting enzyme inhibitors coronary artery decrease des-Argº-BK diabetic disease distensibility doses drugs effect of ACE effect of angiotensin enalapril endothelial cells Engl essential hypertension Evans blue experimental function Gavras gene polymorphism genotype hemodynamic human hypertensive patients increase inhibition kidney kinins left ventricular hypertrophy lisinopril losartan mechanisms metabolism of BK microalbuminuria microcirculation microcirculation networks modulation mortality myocardial infarction neutral endopeptidase nitric oxide normotensive peptide perindopril Pharmacology placebo plasma quinapril ramipril reduction renal renin renin-angiotensin system response role Safar sodium spontaneously hypertensive rats structure studies suppl sympathetic therapy tion tissue treatment trials vitro vivo