© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Increased expression of cardiac angiotensin II type 1 (AT1) receptors decreases myocardial microvessel density after experimental myocardial infarction
aThoraxcenter, Department of Cardiology, Hanzeplein 1, 9713 GZ (PO Box 30.001, 9700 RB), University Hospital, Groningen, The Netherlands
bDepartment of Clinical Pharmacology, University Hospital, Groningen, The Netherlands
cDepartment of Pathology, University Hospital, Groningen, The Netherlands
dSection of Pharmacology, National Institutes of Mental Health, Bethesda, MD, USA
eDepartment of Internal Medicine/COEUR, University Hospital Dijkzigt, Rotterdam, The Netherlands
* Corresponding author. Tel.: +31-50-361-2355; fax: +31-50-361-4391. d.j.van.veldhuisen{at}thorax.azg.nl
Objective: To study the effects of increased levels of myocardial angiotensin II type 1 (AT1) receptor on microvascular growth following myocardial infarction (MI). Methods: MI was created in transgenic rats (TGR) with a cardioselective overexpression of the AT1 receptor. We used Sprague–Dawley (SD) rats as controls. Some of the rats were treated with the selective AT1 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 AT1 receptor blockade. Furthermore, MI decreased microvessel density in the non-infarcted myocardium (SD MI: 1653±37/mm2, P<0.01 vs. sham-operated controls), however, microvessel density decreased significantly more in TGR with MI (1298±33/mm2, P<0.01 vs. SD MI). AT1 receptor blockade restored microvessel density (SD MI Los: 2046±195/mm2; TGR MI Los: 1742±47/mm2; P<0.01 vs. untreated). The differences in microvessel density were still present after correction for LV hypertrophy. The increase in microvessel density after AT1 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 AT1 receptor is overexpressed, and this is amenable to AT1 receptor blockade. This suggests that efficacy of AT1 receptor blockers post-MI may not only be due to attenuation of LV remodeling, but also to a stimulatory effect on angiogenesis.
KEYWORDS Angiotensin; Growth factors; Infarction; Microcirculation; Receptors; Renin angiotensin system
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