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  • Title: Historical development of losartan (DuP 753) and angiotensin II receptor subtypes.
    Author: Wong PC, Timmermans PB.
    Journal: Blood Press Suppl; 1996; 3():11-4. PubMed ID: 8973760.
    Abstract:
    Angiotensin II is an active peptide of the renin-angiotensin system, whose biological actions are mediated through cell surface receptors. It is an important hormone in the regulation of blood pressure, fluid and electrolyte balance. This report describes the historical development of non-peptide angiotensin II receptor antagonists and angiotensin II receptor subtypes. Previous receptor antagonists for angiotensin II are angiotensin-like peptides with limitations of short duration, lack of oral bioavailability and partial agonistic activity. Recently, we have developed the first long-acting and orally-active non-peptide angiotensin II receptor antagonist losartan (DuP 753) which does not have agonistic activities. The discovery of losartan provides a potentially important therapy for the treatment of hypertension and congestive heart failure. Moreover, the use of losartan and other angiotensin II receptor antagonists in research has rapidly expanded our understanding of the physiological and pathophysiological roles of angiotensin II and led to the identification of receptor subtypes, AT1 and AT2. All the known physiological effects of angiotensin II including vasoconstriction and aldosterone release, which can be inhibited by losartan, are attributable to the AT1 receptor subtype. Whether the AT2 receptors serve any important physiological functions remain to be determined.
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