Severe hyperglycemia: a determinant factor for hypofiltration in alloxan diabetic rats.
The relationships among glomerular filtration rate, renal plasma flow and extracellular fluid volume were investigated in control and severely hyperglycemic (442+/-33 mg/dl) untreated, alloxan diabetic ats. Most of diabetic animals showed significant lower values of inulin clearance (diabetics, 0.55+/-0.07 ml/min.100 g; controls, 0.97+/-0.04) and p-aminohippurate clearance (diabetics, 2.11+/-0.39 ml/min.100 g; controls, 3.93+/-0.25). Diabetic rats exhibited reduced efficiency in tubular Na(+) reabsorption, increased urinary Na(+) excretion (diabetics, 3.12+/-0.27 mEq/day; controls, 1.25+/-0.14) and diminished values of plasma renin activity (diabetics, 3.34+/-0.44 ng/ml.h; controls, 8.64+/-0.79). Significant negative correlations were found between glycemia and renal hemodynamic variables. Acute overload with glucose further decreased these variables in both groups: inulin clearance in diabetics vs. controls, 0.26+/-0.04 vs. 0.44+/-0.05 ml/min.100 g; p-aminohippuric acid clearance in diabetics vs. controls, 1.09+/-0.20 vs. 1.55+/-0.21 ml/min.100 g. We conclude that chronically hyperglycemic alloxan diabetic rats showed diminished glomerular filtration rates (inulin clearance), renal plasma flow ( p-aminohippurate clearance) and extracellular fluid volume associated with urinary Na(+) losses and alterations in the renin-angiotensin system. Decreased renin-angiotensin system activity might reduce aldosterone secretion, which in turn could result in (successively) urinary sodium loss, extracellular fluid volume contraction and reductions in glomerular filtration and renal plasma flow.
Di Loreto
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Bone Biology Laboratory, Faculty of Medical Sciences, Rosario National University, Santa Fe 3100, 2000 Rosario, Argentina.
Moreno
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HS
Puche
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RC
Locatto
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ME
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000097:blood / Q000503:physiopathology; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D011919:Rats, Inbred Strains; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D001786:Blood Glucose; D010130:p-Aminohippuric Acid