|Angiotensin converting enzyme 2 contributes to sex differences in the development of obesity hypertension in C57BL/6 mice.|
|PMID: 22460555 Owner: NLM Status: MEDLINE|
|OBJECTIVE: Obesity promotes hypertension, but it is unclear if sex differences exist in obesity-related hypertension. Angiotensin converting enzyme 2 (ACE2) converts angiotensin II (AngII) to angiotensin-(1-7) (Ang-[1-7]), controlling peptide balance. We hypothesized that tissue-specific regulation of ACE2 by high-fat (HF) feeding and sex hormones contributes to sex differences in obesity-hypertension.
METHODS AND RESULTS: HF-fed females gained more body weight and fat mass than males. HF-fed males exhibiting reduced kidney ACE2 activity had increased plasma angiotensin II levels and decreased plasma Ang-(1-7) levels. In contrast, HF-fed females exhibiting elevated adipose ACE2 activity had increased plasma Ang-(1-7) levels. HF-fed males had elevated systolic and diastolic blood pressure that were abolished by losartan. In contrast, HF-fed females did not exhibit increased systolic blood pressure until females were administered the Ang-(1-7) receptor antagonist, D-Ala-Ang-(1-7). Deficiency of ACE2 increased systolic blood pressure in HF-fed males and females, which was abolished by losartan. Ovariectomy of HF-fed female mice reduced adipose ACE2 activity and plasma Ang-(1-7) levels, and promoted obesity-hypertension. Finally, estrogen, but not other sex hormones, increased adipocyte ACE2 mRNA abundance.
CONCLUSIONS: These results demonstrate that tissue-specific regulation of ACE2 by diet and sex hormones contributes to sex differences in obesity-hypertension.
|Manisha Gupte; Sean E Thatcher; Carine M Boustany-Kari; Robin Shoemaker; Frederique Yiannikouris; Xuan Zhang; Michael Karounos; Lisa A Cassis|
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|Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-03-29|
|Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 32 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2012 Jun|
|Created Date: 2012-05-17 Completed Date: 2012-07-13 Revised Date: 2014-09-18|
Medline Journal Info:
|Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States|
|Languages: eng Pagination: 1392-9 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
Adipocytes / enzymology
Angiotensin I / blood
Angiotensin II / blood
Angiotensin II Type 1 Receptor Blockers / pharmacology
Blood Pressure* / drug effects
Disease Models, Animal
Estrogens / metabolism
Gene Expression Regulation, Enzymologic
Hypertension / drug therapy, enzymology, etiology*, genetics, physiopathology
Losartan / pharmacology
Mice, Inbred C57BL
Obesity / complications*, enzymology, etiology, genetics, physiopathology
Peptide Fragments / blood
Peptidyl-Dipeptidase A / deficiency, genetics, metabolism*
Progesterone / metabolism
Proto-Oncogene Proteins / antagonists & inhibitors, metabolism
RNA, Messenger / metabolism
Receptors, G-Protein-Coupled / antagonists & inhibitors, metabolism
Testosterone / metabolism
|F32HL095281/HL/NHLBI NIH HHS; HL73085/HL/NHLBI NIH HHS; P20 GM103527/GM/NIGMS NIH HHS; P20 GM103527-05/GM/NIGMS NIH HHS; P20RR021954/RR/NCRR NIH HHS; R01 HL073085/HL/NHLBI NIH HHS; R01 HL073085-04/HL/NHLBI NIH HHS|
|0/Angiotensin II Type 1 Receptor Blockers; 0/Estrogens; 0/Peptide Fragments; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 0/Receptors, G-Protein-Coupled; 0/angiotensin I (1-7); 0/proto-oncogene proteins c-mas-1; 11128-99-7/Angiotensin II; 3XMK78S47O/Testosterone; 4G7DS2Q64Y/Progesterone; 9041-90-1/Angiotensin I; EC 188.8.131.52/Peptidyl-Dipeptidase A; EC 3.4.17.-/angiotensin converting enzyme 2; JMS50MPO89/Losartan|
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