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 (FENa) 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 (delta -21 +/- 2, delta -10 +/- 2 mmHg, respectively; P < 0.05) with an accompanying fall in FENa (delta -0.10 +/- 0.05, delta -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 FENa (delta 0.13 +/- 0.04, delta 0.95 +/- 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 FENa (delta 1.90 +/- 0.26, delta 1.40 +/- 0.56%, respectively; P < 0.05). Although systemic infusion of losartan decreased MAP (delta -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.(ABSTRACT TRUNCATED AT 250 WORDS)
Peng
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Y
Department of Physiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Knox
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FG
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004039:Diet, Sodium-Restricted; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D019808:Losartan; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
D001713:Biphenyl Compounds; D007093:Imidazoles; D014677:Pharmaceutical Vehicles; D013777:Tetrazoles; D000804:Angiotensin II; D012965:Sodium Chloride; D019808:Losartan