Key result
Specific CNS blockade of AT1 receptors with icv losartan early post-MI effectively ameliorates LV systolic dysfunction in rats, with effects remaining for at least 2 weeks after withdrawal.
Why the study?
Does central nervous system AT1 receptor blockade with icv losartan ameliorate LV dysfunction in rats post-MI after treatment withdrawal?
Does central nervous system AT1 receptor blockade with icv losartan ameliorate LV dysfunction in rats post-MI after treatment withdrawal?
Central nervous system AT1 receptor blockade early post-MI provides prolonged amelioration of LV systolic dysfunction in rats, persisting even after treatment withdrawal.
CNS AT1 blockade merits further preclinical study post-MI; leaves open human translation and should not change practice.
In rats post‐MI, LV dysfunction is attenuated by CNS AT 1 receptor blockade with icv infusion of losartan at doses which are ineffective when administered peripherally. The present study tested whether after withdrawal of the blockade these effects of icv losartan continue. As of 2 days after coronary artery ligation, Wistar rats were infused icv via osmotic minipumps with losartan (1 mg/kg/d) or vehicle, or injected sc daily with losartan (100 mg/kg/d), for 4 wks. Rats with sham ligation served as control. Echocardiography was performed at 4 wks. Two wks after withdrawal of losartan treatment, echo was repeated and LV function assessed with a Millar catheter. These results indicate that in Wistar rats, in contrast to general blockade specific CNS blockade of AT 1 receptors early post MI effectively ameliorates LV systolic dysfunction, and these effects remain for at least 2 weeks after withdrawal of icv losartan. Supported by a grant from Heart Stoke Foundation of Ontario.
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Huang et al. (2008) studied Congestive heart failure post myocardial infarction. Intracerebroventricular (icv) infusion of losartan vs. Vehicle or sham ligation was evaluated on LV systolic dysfunction assessed by echocardiography and Millar catheter. Specific CNS blockade of AT1 receptors with icv losartan early post-MI effectively ameliorates LV systolic dysfunction in rats, with effects remaining for at least 2 weeks after withdrawal.
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