Prolonged amelioration of LV dysfunction after withdrawal of chronic CNS blockade of AT 1 receptors in rats with CHF post MI

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.