title: Gene expression, function and ischemia tolerance in male and female rat hearts after sub-toxic levels of angiotensin II.
abstract: To examine the response to chronic high-dose angiotensin II (Ang II) and a proposed milder response in female hearts with respect to gene expression and ischemic injury. Female and male litter-matched rats were treated with 400 ng kg(-1) min(-1) Ang II for 14 days. Hearts were isolated, subjected to 30-min ischemia and 30-min reperfusion in combination with functional monitoring and thereafter harvested for gene expression, WB and histology. Ang II-treated hearts showed signs of non-hypertrophic remodeling and had significantly higher end diastolic pressure after reperfusion, but no significant gender difference was detected. Ang II increased expression of genes related to heart function (ANF, β-MCH, Ankrd-1, PKC-α, PKC-δ TNF-α); fibrosis (Col I-α1, Col III-α1, Fn-1, Timp1) and apoptosis (P53, Casp-3) without changing heart weight but with 68% increase in collagen content. High (sub-toxic) dose of Ang II resulted in marked heart remodeling and diastolic dysfunction after ischemia without significant myocyte hypertrophy or ventricular chamber dilatation. Although there were some gender-dependent differences in gene expression, female gender did not protect against the overall response.
authors.affiliation: Cardiovascular Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Norway. belal.aljabri@uit.no
authors.forename: M B
authors.initials: MB
authors.lastname: Aljabri
authors.forename: T
authors.initials: T
authors.lastname: Lund
authors.forename: A C
authors.initials: AC
authors.lastname: Höper
authors.forename: T V
authors.initials: TV
authors.lastname: Andreasen
authors.forename: S
authors.initials: S
authors.lastname: Al-Saad
authors.forename: S
authors.initials: S
authors.lastname: Lindal
authors.forename: K
authors.initials: K
authors.lastname: Ytrehus
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation; D015918:Infusion Pumps, Implantable; D055104:Infusions, Subcutaneous; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D020127:Recovery of Function; D012737:Sex Factors; D013997:Time Factors; D016277:Ventricular Function, Left / Q000235:genetics*; D017725:Ventricular Pressure / Q000235:genetics
chemical_list: D000804:Angiotensin II; D003094:Collagen