title: Differential regulation of circulating and renal ACE2 and ACE in hypertensive mRen2.Lewis rats with early-onset diabetes.
abstract: We examined the impact of early diabetes on the circulating and kidney renin-angiotensin system (RAS) in male and female mRen2.Lewis (mRen2) hypertensive rats. Diabetes (DB) was induced by streptozotocin (STZ; 65 mg/kg) at 11 wk of age for 4 wk without insulin replacement. Systolic blood pressures were not increased in DB males or females compared with controls (CON). Circulating angiotensin-converting enzyme 2 (ACE2) increased ninefold (P < 0.05) in DB females and threefold (P < 0.05) in DB males, but circulating ACE and ANG II were higher in the DB groups. Serum C-reactive protein was elevated in DB females but not DB males, and the vascular responses to acetylcholine and estradiol were attenuated in the DB females. Proteinuria, albuminuria, and angiotensinogen excretion increased to a similar extent in both DB females and males. Glomerular VEGF expression also increased to a similar extent in both DB groups. Renal inflammation (CD68(+)cells) increased only in DB females although males exhibited greater inflammation that was not different with DB. Cortical ACE2 did not change in DB females but was reduced (30%) in DB males. Renal neprilysin activity (>75%, P < 0.05) was markedly reduced in the DB females to that in the DB and CON males. ACE activity was significantly lower in both female (75%, P < 0.05) and male (50%; P < 0.05) DB groups, while cortical ANG II and Ang-(1-7) levels were unchanged. In conclusion, female mRen2 rats are not protected from vascular damage, renal inflammation, and kidney injury in early STZ-induced diabetes despite a marked increase in circulating ACE2 and significantly reduced ACE within the kidney.
authors.affiliation: Hypertension and Vascular Research Center, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA.
authors.forename: Liliya M
authors.initials: LM
authors.lastname: Yamaleyeva
authors.forename: Shea
authors.initials: S
authors.lastname: Gilliam-Davis
authors.forename: Igor
authors.initials: I
authors.lastname: Almeida
authors.forename: K Bridget
authors.initials: KB
authors.lastname: Brosnihan
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Lindsey
authors.forename: Mark C
authors.initials: MC
authors.lastname: Chappell
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000235:genetics; D005260:Female; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D015260:Neprilysin / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D012083:Renin / Q000235:genetics* / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects; D012727:Sex Characteristics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D000803:Angiotensin I; D000804:Angiotensin II; D000085962:Angiotensin-Converting Enzyme 2; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D002097:C-Reactive Protein; D003094:Collagen; D015260:Neprilysin; D010446:Peptide Fragments; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D042461:Vascular Endothelial Growth Factor A; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C535029:Ren2 protein, rat; C000705307:ACE2 protein, human; C000705329:Ace2 protein, rat; C118790:angiotensin I (1-7)