Time-course reduction of renal function in rats on high sodium intake: acute reversal by potassium canrenoate.
1. Time course of renal alterations associated with long-term (since weaning) administration of a high sodium (HS, 8% NaCl) diet was assessed in Sprague-Dawley rats. Reversal by acute administration of the mineralocorticoid receptor antagonist, potassium canrenoate (40 mg/kg, i.p.) or the type 1 angiotensin II receptor antagonist, losartan (10 mg/kg, i.v.), was evaluated at the age of 5 months (i.e. after 21 weeks of HS feeding). 2. High sodium intake had no detectable effect on blood pressure; however, albuminuria was always higher in the HS than control group. Glomerular filtration rate, renal plasma flow and filtration fraction decreased significantly after 12 weeks of HS diet by approximately 50, 30 and 20%, respectively. Canrenoate was effective and markedly reversed the renal hypofiltration associated with HS feeding without change in systemic blood pressure. In contrast, losartan reduced blood pressure and it was devoid of a beneficial effect on renal function. 3. The present observations indicate that hypofiltration and hypoperfusion of the kidney occurred progressively and require a long period of exposure to a high sodium intake. Albuminuria, which increased before detectable changes in renal function, may represent an early marker of renal dysfunction. The beneficial effect of acute administration of potassium canrenoate favours the participation of aldosterone, at least partially, in the sustained deterioration of renal function after 21 weeks of high sodium feeding.
Rugale
Caroline
C
Groupe Rein et Hypertension, Montpellier University, Montpellier, France.
Cordaillat
Magali
M
Mimran
Albert
A
Jover
Bernard
B
D000419:Albuminuria / Q000139:chemically induced; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002191:Canrenoic Acid / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary / Q000009:adverse effects*
D012982:Sodium, Dietary; D002191:Canrenoic Acid; D019808:Losartan