This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sibinga, N. E. S. Articles by Ware, J. A. Search for Related Content PubMed PubMed Citation Articles by Sibinga, N. E. S. Articles by Ware, J. A. Related Collections ACE/Angiotension receptors

(Circulation Research. 2000;87:523.)
© 2000 American Heart Association, Inc.

Editorial

A Pair of ACEs, for Openers?

Nicholas E. S. Sibinga, J. Anthony Ware

From the Cardiovascular Division, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.

Correspondence to Nicholas E.S. Sibinga, MD, or J. Anthony Ware, MD, Cardiovascular Division, Albert Einstein College of Medicine, Forchheimer Bldg, G-46, 1300 Morris Park Blvd, Bronx, NY 10461. E-mail nsibinga@aecom.yu.edu or jaware@aecom.yu.edu

Key Words: enzymes • metabolism • drug therapy • angiotensin-converting enzyme • angiotensin

	Introduction

 
The renin-angiotensin system (RAS) has provided bountiful material for investigation by basic scientists and clinicians for more than 100 years. Renin, first identified in 1898 as a pressor substance present in kidney extracts,¹ sits at the top of an enzymatic cascade that, in its simplest form, is now broadly known: renin cleaves the circulating precursor, angiotensinogen, to release the inactive angiotensin I, which is in turn cleaved by angiotensin-converting enzyme (ACE) to release angiotensin II, a very potent vasoconstrictor. This ability of ACE, initially purified from plasma, to mediate the cleavage of the decapeptide angiotensin I (Ang1-10) to the octapeptide angiotensin II (Ang1-8) was reported in 1956.² Localization of the bulk of this conversion reaction to tissue ACE, particularly in the pulmonary vascular bed, was demonstrated in 1968.³

Despite the central position ACE has assumed as a target for antihypertensive therapies, the significance of angiotensin in blood pressure regulation was not fully appreciated until the identification of pharmacological inhibitors of ACE (for review, see Vane⁴ ). The first of these, a nonapeptide called teprotide,⁵ was derived from an extract of venom from the Brazilian viper Bothrops jararaca; once the link between angiotensin and hypertension was demonstrated through investigative⁶ and clinical⁷ administrations of teprotide, the utility of ACE inhibition was clear. Positing similarities of the active site of ACE to that of carboxypeptidase-A, investigators at the Squibb Institute for Medical Research designed, synthesized, and tested a series of about 60 compounds, an effort that led to the identification of captopril.⁸ . . . [Full Text of this Article]