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  • Title: Angiotensin II inhibition during myocardial ischemia-reperfusion in dogs: effects on leukocyte infiltration, nitric oxide synthase isoenzymes activity and left ventricular ejection fraction.
    Author: de Gusmão FM, Becker C, Carvalho MH, Barros LF.
    Journal: Int J Cardiol; 2005 Apr 28; 100(3):363-70. PubMed ID: 15837077.
    Abstract:
    Leukocyte infiltration and activation in myocardial reperfusion injury may be modulated by nitric oxide synthase isoforms. Angiotensin II influences leukocyte activation directly or by nitric oxide generation mechanisms. The effects of angiotensin II inhibition before reperfusion on myocardial function, leukocyte accumulation and nitric oxide synthase were evaluated on three groups of eight dogs. They were submitted to occlusion of the left anterior descending coronary artery for 90 min, followed by 120 min of reperfusion. The first group received captopril, the second losartan and the third received normal saline solution. Left ventricular ejection fraction significantly improved after reperfusion in the groups under captopril (15+/-5.1%, p=0.029) and losartan (16+/-4.3%, p=0.014) when compared to the control group (7+/-2.5%). Myeloperoxidase activity was significantly lower in captopril group (6.6+/-1.0 U/100 mg, p=0,036) and losartan (6.8+/-1.7 U/100 mg, p=0.044) than in the control group (12.5+/-4.7 U/100 mg). Significant difference on constitutive nitric oxide synthase activity was not observed when all three groups were compared simultaneously (10.1+/-1.8 versus 8.5+/-1.3 versus 7.3+/-1.9 fM/mg/min, p=0.447). Inducible nitric oxide synthase activity was significantly lower in the losartan group (9.0+/-4.1 fM/mg/min) than in the captopril (29.2+/-5.1 fM/mg/min, p=0.0001) and control groups (26.2+/-4.6 fM/mg/min, p=0.0001). Angiotensin II inhibition reduced leukocyte infiltration and improved left ventricular ejection fraction during reperfusion by angiotensin-converting enzyme inhibition or by angiotensin II type 1 receptor blocker. This was observed without influencing the constitutive nitric oxide synthase activity. Only losartan reduced inducible nitric oxide synthase activity but did not influence the leukocyte infiltration and myocardial contractile function.
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