Comparison of systemic and direct intrarenal angiotensin II blockade on sodium excretion in rats

To dissociate the renal effects from the systemic effects of angiotensin II blockade, the present study was designed to determine the effects of systemic and renal interstitial infusion of the specific angiotensin II (ANG II) receptor antagonist, losartan, on blood pressure and sodium excretion in rats fed a low-, normal, or high-sodium diet. Fractional sodium excretion (FE_Na) and mean arterial pressure (MAP) were measured in rats before and during systemic infusion of losartan (10 mg/kg) or renal interstitial infusion of losartan (3 mg/kg) by means of a chronically implanted matrix. In rats fed a low- or normal sodium diet, systemic infusion of losartan markedly decreased MAP (Δ -21 ± 2, Δ - 10 ± 2 mmHg, respectively; P < 0.05) with an accompanying fall in FE_Na (Δ -0.10 ± 0.05, Δ -0.91 ± 0.40%, respectively; P < 0.05). In contrast, preferential blockade of renal ANG II with renal interstitial losartan infusion resulted in an increase in FE_Na (Δ0.13 ± 0.04, Δ0.95 ± 0.45%, respectively; P < 0.05) and no significant change in MAP. In rats fed a high-sodium diet, both systemic and renal interstitial infusion of losartan increased FE_Na (Δ1.90 ± 0.26, Δ1.40 ± 0.56%, respectively; P < 0.05). Although systemic infusion of losartan decreased MAP (Δ -4.4 ± 0.6 mmHg, P < 0.05) in rats fed a high-sodium diet, the reduction in MAP was much less than that in rats fed a low- and normal sodium diet. In conclusion, in rats fed a low- or normal sodium diets, systemic ANG II blockade reduced both arterial blood pressure and sodium excretion, whereas intrarenal ANGII blockade had no effect on blood pressure and increased sodium excretion. In contrast, both systemic and intrarenal ANG II blockade increased sodium excretion without marked effects on blood pressure in rats fed a high-sodium diet.