title: Increased expression of cardiac angiotensin II type 1 (AT(1)) receptors decreases myocardial microvessel density after experimental myocardial infarction.
abstract: OBJECTIVE
  To study the effects of increased levels of myocardial angiotensin II type 1 (AT(1)) receptor on microvascular growth following myocardial infarction (MI).
  
  
  METHODS
  MI was created in transgenic rats (TGR) with a cardioselective overexpression of the AT(1) receptor. We used Sprague-Dawley (SD) rats as controls. Some of the rats were treated with the selective AT(1) receptor blocker losartan (Los). Rats were sacrificed after 3 weeks.
  
  
  RESULTS
  MI caused left ventricular (LV) hypertrophy and LV dysfunction in both SD and TGR, which was prevented by AT(1) receptor blockade. Furthermore, MI decreased microvessel density in the non-infarcted myocardium (SD MI: 1653+/-37/mm(2), P<0.01 vs. sham-operated controls), however, microvessel density decreased significantly more in TGR with MI (1298+/-33/mm(2), P<0.01 vs. SD MI). AT(1) receptor blockade restored microvessel density (SD MI Los: 2046+/-195/mm(2); TGR MI Los: 1742+/-47/mm(2); P<0.01 vs. untreated). The differences in microvessel density were still present after correction for LV hypertrophy. The increase in microvessel density after AT(1) receptor blockade was not accompanied by increased myocardial vascular endothelial growth factor (VEGF) levels. Microvessel density correlated with parameters of myocardial stretch, such as LV end-diastolic pressure (-0.681, P<0.001) and N-ANP (-0.424, P=0.01).
  
  
  CONCLUSIONS
  Microvessel density after MI is decreased when the AT(1) receptor is overexpressed, and this is amenable to AT(1) receptor blockade. This suggests that efficacy of AT(1) receptor blockers post-MI may not only be due to attenuation of LV remodeling, but also to a stimulatory effect on angiogenesis.
authors.affiliation: Thoraxcenter, Department of Cardiology, Hanzeplein 1, 9713 GZ, PO Box 30.001, 9700 RB, University Hospital, Groningen, The Netherlands.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.forename: Yigal M
authors.initials: YM
authors.lastname: Pinto
authors.forename: Albert J H
authors.initials: AJ
authors.lastname: Suurmeijer
authors.forename: Saraswati
authors.initials: S
authors.lastname: Pokharel
authors.forename: Egbert
authors.initials: E
authors.lastname: Scholtens
authors.forename: Michael
authors.initials: M
authors.lastname: Humler
authors.forename: Juan M
authors.initials: JM
authors.lastname: Saavedra
authors.forename: Frans
authors.initials: F
authors.lastname: Boomsma
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D030801:Animals, Genetically Modified; D009320:Atrial Natriuretic Factor / Q000097:blood; D001835:Body Weight; D003326:Coronary Circulation; D016228:Endothelial Growth Factors / Q000378:metabolism; D006352:Heart Ventricles / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D009929:Organ Size; D011498:Protein Precursors / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism* / Q000502:physiology; D012084:Renin-Angiotensin System; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000503:physiopathology*; D020257:Ventricular Remodeling
chemical_list: D057911:Angiotensin Receptor Antagonists; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C099254:N-terminal proatrial natriuretic peptide; D011498:Protein Precursors; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009320:Atrial Natriuretic Factor