Changing dietary sodium alters the cardiovascular response to losartan regardless of initial state of the RAS

• Published in: The FASEB journal 2006-03, Vol.20 (4), p.A756-A756
• Main Authors: Nahey, David B, Collister, John P
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.20.4.A756-b

We have previously demonstrated a profound hypotensive response to the 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 hypothesized 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 radio‐telemetry transducers for MAP monitoring and venous catheters for infusion were placed on either a 0.4% (LosNO, n = 3) or 4.0% (LosHI, n = 3) salt diet. After a 3 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 3 day recovery period. At the start of losartan infusion MAP was observed to be similar between LosNO rats (98 ± 5 mmHg) and LosHI rats (104 ± 3 mmHg). By day 7 of the first 10 day protocol, MAP in LosNO rats had fallen to 72 ± 8 mmHg while decreasing to only 94 ± 3 mmHg in LosHI rats. Five days after switching diets, MAP in LosNO rats had risen back to 93 ± 7 mmHg, while MAP in LosHI rats had further decreased to 80 ± 3 mmHg. These results do not support our hypothesis, suggesting that changing dietary sodium can alter the cardiovascular response to losartan regardless of the initial state of the RAS.