title: Pregnancy protects against antiangiogenic and fibrogenic effects of angiotensin II in rat hearts.
abstract: OBJECTIVE
  To investigate the difference between physiological and pathological cardiac remodelling induced, respectively, by pregnancy and angiotensin (Ang) II, and to test the hypothesis that pregnancy protects against Ang II effects.
  
  
  METHODS
  Female Wistar rats, pregnant (n = 12) and non-pregnant (n = 12), were implanted with mini-pumps containing saline (sham) or 150 ng kg(-1) min(-1) Ang II. Ten days later echocardiography and blood pressure measurement were performed. Expression of 22 genes was assessed using RT-PCR. Microscopic sections of LV were prepared to determine collagen content (Sirius Red staining), vessel density (β-actin immunolabelling) and myocytes diameter (Toluidine Blue).
  
  
  RESULTS
  Heart weight (HW) was increased in Ang II treated groups compared with their controls. Furthermore, HW of Ang II treated pregnant rats (1.0 ± 0.03 g) was higher than that in non-pregnant sham (0.7 ± 0.02 g), pregnant (0.8 ± 0.01 g) and Ang II treated non-pregnant (0.8 ± 0.02 g) rats. Relative LV wall thickness showed similar pattern. Aortic pressure was significantly increased in Ang II groups. Collagen content was increased in Ang II (4.0 ± 0.5%) compared with sham (1.5 ± 0.1%) but reduced again when treated rats were pregnant (2.8 ± 0.4%). Vessel density was reduced by 47.8% after Ang II treatment in non-pregnant and by only 13.9% in pregnant rats. Gene expression analysis showed increased expression of atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), anykrin repeat domain-containing protein 1 (Ankrd-1), protein kinase C-α and -δ and tumour suppressor gene TP53 (p53) in Ang II treated groups and upregulation of ANF, BNP and Ankrd-1 remained when pregnancy was combined with Ang II. Pregnancy reduced expression of: α-myosin heavy chain, tumour necrosis factor-α, p53, endothelial nitric oxide synthase and inducible nitric oxide synthase.
  
  
  CONCLUSIONS
  Pregnancy seems to counteract the detrimental effects of Ang II on fibrosis and angiogenesis in heart. In addition, pregnancy and Ang II lead to partly opposite changes in the expression of some genes important for heart function.
authors.affiliation: Cardiovascular Research Group, Department of Medical Biology, Faculty of Health Science, University of Tromsø, Norway. belal.aljabri@uit.no
authors.forename: M B
authors.initials: MB
authors.lastname: Aljabri
authors.forename: N T
authors.initials: NT
authors.lastname: Songstad
authors.forename: T
authors.initials: T
authors.lastname: Lund
authors.forename: M C
authors.initials: MC
authors.lastname: Serrano
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: V
authors.initials: V
authors.lastname: Sitras
authors.forename: G
authors.initials: G
authors.lastname: Acharya
authors.forename: K
authors.initials: K
authors.lastname: Ytrehus
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003094:Collagen / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling
chemical_list: D000804:Angiotensin II; D003094:Collagen