title: New insights into the importance of aminopeptidase A in hypertension.
abstract: The renin-angiotensin system (RAS) plays an important role in the maintenance of normal blood pressure and the etiology of hypertension; however, minimal attention has been paid to the degradation of the effector peptide, angiotensin II (AngII). Since aminopeptidase A (APA)-deficient mice develop hypertension APA appears to be an essential enzyme in the control of blood pressure via degradation of AngII. The robust hypertension seen in the spontaneously hypertensive rat (SHR) is due to activation of the RAS, and an accompanying decrease in kidney APA. Changes in APA have also been measured during the activation of the RAS in the Goldblatt hypertension model and Dahl salt-sensitive (DSS) rat. The DSS rat shows an elevation in renal APA activity at the onset of hypertension suggesting a protective role against elevations in circulating AngII, followed by decreased APA activity with advancing hypertension. Changes seen in human maternal serum APA activity during preeclampsia are similar to changes measured in renal APA in the DSS rat model. APA activity is higher than during normal pregnancy at the onset of preeclampsia, and with advancing preeclampsia (severe preeclampsia) declines below that seen during normal pregnancy. Serum APA activity is also increased during hormone replacement therapy (HRT), perhaps in reaction to elevated levels of AngII. Thus, it appears important to consider the relationship among activation of the RAS, circulating levels of AngII, and the availability of APA in hypertensive disorders.
authors.affiliation: Department of Medical Science of Proteases, Nagoya University, Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Mizutani
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ishii
authors.forename: Akira
authors.initials: A
authors.lastname: Hattori
authors.forename: Seiji
authors.initials: S
authors.lastname: Nomura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Numaguchi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kobayshi
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: John W
authors.initials: JW
authors.lastname: Wright
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D043384:Glutamyl Aminopeptidase / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D011225:Pre-Eclampsia / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D000804:Angiotensin II; D043384:Glutamyl Aminopeptidase