What is the effect of Losartan (angiotensin II receptor antagonist) on urine sodium excretion?

Effect of Losartan on Urine Sodium Excretion

Losartan significantly increases urinary sodium excretion, particularly in individuals on a low-sodium diet, through its action as an angiotensin II receptor antagonist. 1

Mechanism of Action

Losartan works by blocking the angiotensin II type 1 (AT1) receptor, which has several effects on sodium handling in the kidneys:

1. Efferent Arteriole Vasodilation: Losartan antagonizes angiotensin II, causing efferent vasodilation, leading to higher renal blood flow 2

2. Reduced Sodium Reabsorption: By blocking the effects of angiotensin II, losartan reduces sodium avidity (retention) in the kidneys 2

3. Natriuretic Effect: This leads to increased urinary sodium excretion, which is most pronounced under low-sodium dietary conditions 3

Evidence on Sodium Excretion

Research demonstrates that losartan has significant effects on urinary sodium excretion:

• In healthy volunteers on a low-sodium diet (50 mmol/day), a single 100 mg dose of losartan markedly increased urinary sodium excretion from 115 ± 9 to 207 ± 21 μmol/min (p < 0.05) 3

• This natriuretic effect was less pronounced in subjects on a high-sodium diet, suggesting that the sodium-excreting properties of losartan are most evident during sodium restriction 3

• The effect appears to be independent of changes in the early proximal tubule, as the fractional excretion of endogenous lithium remained unchanged 3

Associated Effects

Along with increased sodium excretion, losartan administration is associated with:

• Increased urine flow rate (from 10.5 ± 0.4 to 13.1 ± 0.6 mL/min, p < 0.05) 3
• Increased urinary potassium excretion (from 117 ± 6.9 to 155 ± 11 μmol/min) 3
• Increased excretion of chloride, magnesium, calcium, and phosphate 3
• Uricosuric properties (increased uric acid excretion) regardless of sodium diet status 1, 3

Clinical Implications

The natriuretic effect of losartan has important clinical implications:

• Heart Failure Management: By promoting sodium excretion, losartan can help reduce congestion in heart failure patients 2

• Blood Pressure Control: The natriuretic effect contributes to blood pressure reduction, especially when combined with diuretics 4

• Kidney Protection: Losartan's ability to reduce sodium retention may contribute to its renoprotective effects in chronic kidney disease 5

• Reduced Aldosterone Levels: Losartan reduces both basal and angiotensin II-stimulated aldosterone levels under low salt conditions, further contributing to sodium excretion 6

Practical Considerations

When using losartan for its natriuretic effects:

• The effect is most pronounced in patients on sodium-restricted diets 3
• The natriuretic effect contributes to losartan's antihypertensive properties
• Monitoring of electrolytes may be warranted, especially when combined with diuretics
• The sodium-excreting effect may be particularly beneficial in conditions characterized by sodium retention (heart failure, cirrhosis, nephrotic syndrome)

In summary, losartan significantly increases urinary sodium excretion through its action as an angiotensin II receptor antagonist, with this effect being most pronounced in individuals on a low-sodium diet.