Increased expression of cardiac angiotensin II type 1 (AT1) receptors decreases myocardial microvessel density after experimental myocardial infarction

被引:50
作者
de Boer, RA
Pinto, YM
Suurmeijer, AJH
Pokharel, S
Scholtens, E
Humler, M
Saavedra, JM
Boomsma, F
van Gilst, WH
van Veldhuisen, DJ
机构
[1] Univ Groningen Hosp, Thoraxctr, Dept Cardiol, NL-9713 GZ Groningen, Netherlands
[2] Univ Groningen Hosp, Dept Clin Pharmacol, Groningen, Netherlands
[3] Univ Groningen Hosp, Dept Pathol, Groningen, Netherlands
[4] NIMH, Pharmacol Sect, Bethesda, MD 20892 USA
[5] Univ Hosp Dijkzigt, COEUR, Dept Internal Med, NL-3015 GD Rotterdam, Netherlands
关键词
angiotensin; growth factors; infarction; microcirculation; receptors; renin angiotensin system;
D O I
10.1016/S0008-6363(02)00704-6
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: To study the effects of increased levels of myocardial angiotensin II type I (AT,) 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, 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) ,<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, 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, receptor is overexpressed, and this is amenable to AT, receptor blockade. This suggests that efficacy of AT, receptor blockers post-MI may not only be due to attenuation of LV remodeling, but also to a stimulatory effect on angiogenesis. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:434 / 442
页数:9
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