|Local angiotensin II aggravates cardiac remodeling in hypertension.|
|PMID: 20833959 Owner: NLM Status: MEDLINE|
|Angiotensin II (ANG II) contributes to hypertension, cardiac hypertrophy, fibrosis, and dysfunction; however, it is difficult to separate the cardiac effect of ANG II from its hemodynamic action in vivo. To overcome the limitations, we used transgenic mice with cardiac-specific expression of a transgene fusion protein that releases ANG II from cardiomyocytes (Tg-ANG II) and treated them with deoxycorticosterone acetate (DOCA)-salt to suppress their systemic renin-angiotensin system. Using this unique model, we tested the hypothesis that cardiac ANG II, acting on the angiotensin type 1 receptor (AT(1)R), increases inflammation, oxidative stress, and apoptosis, accelerating cardiac hypertrophy and fibrosis. Male Tg-ANG II mice and their nontransgenic littermates (n-Tg) were uninephrectomized and divided into the following three groups: 1) vehicle-treated normotensive controls; 2) DOCA-salt; and 3) DOCA-salt + valsartan (AT(1)R blocker).Under basal conditions, systolic blood pressure (SBP) and cardiac phenotypes were similar between strains. In DOCA-salt hypertension, SBP increased similarly in both n-Tg and Tg-ANG II, and cardiac function did not differ between strains; however, Tg-ANG II had 1) greater ventricular hypertrophy as well as interstitial and perivascular fibrosis; 2) a higher number of deoxynucleotidyl-transferase-mediated dUTP nick end labeling-positive cells and infiltrating macrophages; 3) increased protein expression of NADPH oxidase 2 and transforming growth factor-β(1); and 4) downregulation of phosphatidylinositol 3-kinase (PI 3-kinase) and protein kinase B (Akt) phosphorylation. Valsartan partially reversed these effects in Tg-ANG II but not in n-Tg. We conclude that, when hemodynamic loading conditions remain unchanged, cardiac ANG II does not alter heart size or cardiac functions. However, in animals with hypertension, cardiac ANG II, acting via AT(1)R, enhances inflammation, oxidative stress, and cell death (most likely via downregulation of PI 3-kinase and Akt), contributing to cardiac hypertrophy and fibrosis.|
|Jiang Xu; Oscar A Carretero; Tang-Dong Liao; Hongmei Peng; Edward G Shesely; Junxiao Xu; Thomas S Liu; James J Yang; Timothy L Reudelhuber; Xiao-Ping Yang|
Related Documents :
|23743499 - A prospective evaluation of hemodynamic management in acute spinal cord injury patients.
9277539 - Baroreceptor-independent renal nerve inhibition by intracerebroventricular angiotensin ...
22324419 - Pressure-derived versus pressure wave amplitude-derived indices of cerebrovascular pres...
7895239 - Role of polyamines in hypertension induced by angiotensin ii.
11447089 - Load versus humoral activation in the genesis of early hypertensive heart disease.
18845809 - Angiotensin(1-7) blunts hypertensive cardiac remodeling by a direct effect on the heart.
3653559 - Central role for sodium in the pathogenesis of blood pressure changes independent of an...
22681329 - Relaxation versus fractionation as hypnotic deepening: do they differ in physiological ...
7988129 - Influence of pressure- and flow-triggered synchronous intermittent mandatory ventilatio...
|Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-09-10|
|Title: American journal of physiology. Heart and circulatory physiology Volume: 299 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2010 Nov|
|Created Date: 2010-11-01 Completed Date: 2010-11-29 Revised Date: 2013-05-28|
Medline Journal Info:
|Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States|
|Languages: eng Pagination: H1328-38 Citation Subset: IM|
|Hypertension & Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan 48202-2689, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Angiotensin II Type 1 Receptor Blockers / pharmacology
Apoptosis / physiology
Collagen / metabolism
Desoxycorticosterone / adverse effects, analogs & derivatives
Dinoprost / analogs & derivatives, metabolism
Disease Models, Animal
Heart Rate / physiology
Hypertension / chemically induced, metabolism*, physiopathology
Membrane Glycoproteins / metabolism
Myocardium / metabolism*, pathology
Myocytes, Cardiac / drug effects, metabolism*
NADPH Oxidase / metabolism
Oxidative Stress / physiology
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Receptor, Angiotensin, Type 1 / metabolism
Renin-Angiotensin System / drug effects, physiology
Tetrazoles / pharmacology
Transforming Growth Factor beta1 / metabolism
Valine / analogs & derivatives, pharmacology
|HL-078951/HL/NHLBI NIH HHS; HL-28982/HL/NHLBI NIH HHS|
|0/Angiotensin II Type 1 Receptor Blockers; 0/Membrane Glycoproteins; 0/Receptor, Angiotensin, Type 1; 0/Tetrazoles; 0/Transforming Growth Factor beta1; 11128-99-7/Angiotensin II; 137862-53-4/valsartan; 27415-26-5/8-epi-prostaglandin F2alpha; 551-11-1/Dinoprost; 64-85-7/Desoxycorticosterone; 6E0A168OB8/desoxycortone acetate; 7004-03-7/Valine; 9007-34-5/Collagen; EC 220.127.116.11/Cybb protein, mouse; EC 18.104.22.168/NADPH Oxidase; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 22.214.171.124/Proto-Oncogene Proteins c-akt|
|Am J Physiol Heart Circ Physiol. 2010 Nov;299(5):H1304-6
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Impaired flow-induced dilation of coronary arterioles of dogs fed a low-salt diet: roles of ANG II, ...
Next Document: Delayed activation of caspase-independent apoptosis during heart failure in transgenic mice overexpr...