Effects of different durations of pretreatment with losartan on myocardial infarct size, endothelial function, and vascular endothelial growth factor.
A previous study by our group showed that 10 weeks of pretreatment with losartan reduced myocardial infarct size and arrhythmias in a rat model of ischaemia-reperfusion. However, the effect of a differing time course of pretreatment has not been investigated. 104 Sprague-Dawley rats were randomised to four groups: a control, and three treatment groups in which losartan (40 mg/kg/day) was administered in drinking water for one day, one week, and four weeks respectively. After different durations of pretreatment, the rats were subjected to 17 minutes of left coronary artery occlusion and 120 minutes of reperfusion. Haemodynamic variables were not significantly different between the four groups. Myocardial infarct size was unchanged after one day and one week of pretreatment (52+/-7, 57+/-6% vs.control 55+/-3%), but was significantly reduced by four weeks of pretreatment with losartan (38+/-6, p<0.05). Endothelial-dependent vasorelaxation was significantly increased by four weeks of pretreatment (-81+/-4 vs.-62+7%, p<0.05). As an indicator of ischaemia, vascular endothelial growth factor (VEGF) levels in ischaemic myocardium were decreased after one and four weeks of pretreatment (0.75+/-0.05, 0.58+/-0.10 vs. 1.0, p<0.05,0.01, respectively). In conclusion, losartan has time-dependent cardiovascular protective effects. Four weeks of pretreatment with losartan decreased infarct size and VEGF, and improved endothelial dysfunction.
Zhu
B
B
Department of Medicine, University of California, San Francisco 94143-0124, USA.
Sun
Y
Y
Sievers
R E
RE
Browne
A E
AE
Lee
R J
RJ
Chatterjee
K
K
Parmley
W W
WW
D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D019808:Losartan / Q000494:pharmacology*; D008222:Lymphokines / Q000378:metabolism*; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000804:Angiotensin II; D012083:Renin; D019808:Losartan