title: Developmental expression of ACE2 in the SHR kidney: a role in hypertension?
abstract: The abnormal development of the intrarenal renin-angiotensin system (RAS) is thought contribute to adult-onset hypertension in the spontaneously hypertensive rat (SHR). Angiotensin-converting enzyme 2 (ACE2) is a novel enzyme with complementary actions to that of ACE. Recent studies have shown that ACE2 expression is reduced in the adult SHR. However, its regulation in pre-hypertensive animals is unknown. In this study, we examine the developmental expression of ACE2 in the rodent kidney and its temporal expression, as it relates to the development of hypertension in the SHR model. Kidneys from SHR and normotensive Wistar Kyoto (WKY) rats (n=8-12/group) at birth, 6 weeks of age, and adulthood (80 days) were examined. Gene expression and activity of ACE2 were determined by real-time reverse transcription-polymerase chain reaction and quenched fluorescence assays, respectively. Renal expression was localized by in situ hybridization and immunohistochemistry. The expression and ACE2 activity are significantly increased in the SHR kidney at birth. With the onset of hypertension, the tubular expression of ACE2 falls in SHR compared to WKY and remains reduced in the adult SHR kidney. Glomerular expression is paradoxically increased in the SHR glomerulus. The overall developmental pattern of ACE2 expression in the SHR kidney is also modified, with declining expression over the course of renal development. The developmental pattern of ACE2 expression in the SHR kidney is altered before the onset of hypertension, consistent with the key role of the RAS in the pathogenesis of adult-onset hypertension. Further research is required to distinguish the contribution of these changes to the development and progression of hypertension in this model.
authors.affiliation: Baker Heart Research Institute, St Kilda Central, Melbourne, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Tikellis
authors.forename: M E
authors.initials: ME
authors.lastname: Cooper
authors.forename: K
authors.initials: K
authors.lastname: Bialkowski
authors.forename: C I
authors.initials: CI
authors.lastname: Johnston
authors.forename: W C
authors.initials: WC
authors.lastname: Burns
authors.forename: R A
authors.initials: RA
authors.lastname: Lew
authors.forename: A I
authors.initials: AI
authors.lastname: Smith
authors.forename: M C
authors.initials: MC
authors.lastname: Thomas
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D005786:Gene Expression Regulation; D006977:Hypertension, Renal / Q000201:enzymology* / Q000235:genetics; D007668:Kidney / Q000201:enzymology* / Q000254:growth & development*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2