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Reduced Formation of Ang‐(1–7) by ACE2 in Dorsal Medulla Oblongata of Sprague‐Dawley (SD) and ASrAogen Rats During Aging
Author(s) -
Gegick Stephen,
GarciaEspinosa Maria A.,
Gallagher Patricia E.,
Westwood Brian M.,
Ferrario Carlos M.,
Ganten Detlev,
Chappell Mark C.,
Diz Debra I.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1209-a
Subject(s) - medicine , medulla oblongata , endocrinology , neprilysin , baroreceptor , angiotensin converting enzyme 2 , enzyme , renin–angiotensin system , messenger rna , medulla , chemistry , central nervous system , blood pressure , covid-19 , heart rate , biochemistry , gene , disease , infectious disease (medical specialty)
Angiotensin (Ang) II and Ang‐(1–7) have opposing effects on the baroreceptor reflex; loss of Ang‐(1–7) with effects of Ang II unopposed may account for decreased baroreceptor function during aging. In medulla oblongata, we identified the enzymes present and activities forming Ang‐(1–7) from 125 I‐Ang I or 125 I‐Ang II, how activity changes with aging and how it differs in transgenic rats (ASrAogen) with reduced glial angiotensinogen. Both angiotensin converting enzyme (ACE) 2 and neprilysin (NEP) mRNA as determined using RT‐PCR tended to decrease ~15–20 % during aging (15 wks vs 70 wks of age), with significant reductions for NEP mRNA in older SD rats (p<0.05) and ACE2 mRNA in older ASrAogen rats (p<0.05). ACE mRNA was not different between older and younger animals of either strain and no significant differences in mRNA for the three enzymes were detected between strains. ACE, ACE2 and NEP activities detected in solubilized membranes obtained from dorsal medulla at either age were not different between SD and ASrAogen rats. NEP activity tended to decline during aging in ASrAogen (63%) and SD (40%) animals with ~36% lower ACE2 activity in older rats of both strains. ACE activity did not change with age. The reductions in activity of NEP and ACE2 account for ~40% less overall Ang (1–7) formation in older animals. Thus, NEP and ACE2 are present and active in processing of Ang peptides in rat dorsal medulla. ACE2 appears to be predominant in formation of Ang‐(1–7) and loss of Ang‐(1–7) formation rather than an increase in Ang II may contribute to impaired baroreceptor reflexes in older individuals (Support: HL‐51952; HL‐56973).