Abstract
We have previously demonstrated a profound hypotensive response to the angiotensin II type 1 (AT1)-receptor antagonist losartan in rats consuming a normal salt diet that is not seen in salt-loaded rats, presumably due to a suppression of the renin-angiotensin system (RAS) by high sodium levels. The purpose of the present study was to examine the cardiovascular effects of changing dietary sodium intake during chronic treatment with losartan. We hypothesised that during blockade of AT1-receptors by chronic losartan infusion, when renin levels would be elevated regardless of dietary sodium, changing diets from high to normal or normal to high salt would have no effect on mean arterial pressure (MAP). To test this hypothesis, groups of rats instrumented with radiotelemetry transducers for MAP monitoring and venous catheters for infusion were initially placed on either a 0.4% salt content diet, referred to as Losartan Normal diet - High salt diet (LosN-HI, n = 7), or a 4.0% salt content diet, referred to as Losartan High salt diet - Normal diet (LosHI-N, n = 9). After a thee-day control period, infusion of losartan was begun in all rats (10 mg/kg/day in 7 ml/day isotonic saline i.v.). After 10 days, diets were switched between groups and data were collected for another 10 days, after which losartan infusion was terminated for a 10-day recovery period. At the start of losartan infusion MAP was observed to be similar between LosN-HI rats (101+/-2 mmHg) and LosHI-N rats (101+/-2 mmHg). By day seven of the first 10 day protocol, MAP in LosN-HI rats had fallen to 71+/-4 mmHg while decreasing to 90+/-2 mmHg in LosHI-N rats. Five days after switching diets, MAP in LosN-HI rats had risen back to 85+/-3 mmHg, while MAP in LosHI-N rats had fallen to 75+/-2 mmHg. These results do not support our hypothesis, suggesting that changing dietary sodium can alter the chronic hypotensive response to losartan regardless of the initial state of the RAS.
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