Angiotensin-converting enzyme inhibition ameliorates the defect in glomerular size selectivity in hyponatremic hypertensive syndrome.
The glomerular size-selective properties in a patient with "hyponatremic hypertensive syndrome" were investigated before and after administration of the angiotensin-converting enzyme inhibitor enalapril. Hyponatremic hypertensive syndrome is a rare condition of renovascular hypertension characterized by electrolyte abnormalities (hyponatremia, hypokalemia), polyuria, and high renin activity. In this patient a marked increase in urinary protein excretion was observed. Treatment with enalapril normalized BP, corrected electrolyte abnormalities, and reduced proteinuria. Glomerular filtration rate (GFR), renal plasma flow (RPF), and the clearance of neutral dextrans of graded sizes were measured before and after 6 months of enalapril (20 mg/d) administration. Theoretical analysis of dextran and inulin clearance data with a model of glomerular size selectivity were adopted to separate effects of hemodynamic changes on macromolecule filtration from changes of intrinsic membrane selective properties. After enalapril urinary protein excretion decreased, GFR was unchanged and RPF almost doubled. Fractional clearance values of dextran molecules were markedly elevated in comparison with the corresponding values measured in a group of normal controls and were normalized by enalapril. Theoretical calculation of membrane pore characteristics showed that enalapril treatment reduced the radius of all membrane pores by approximately 1 nm. Altogether these results indicate that enalapril normalized glomerular filtration of neutral macromolecules and circulating proteins in a human condition of angiotensin II-induced proteinuria. Enalapril effectively restored glomerular size-selective function, reducing dimensions of membrane pores, independently of its effect on renal hemodynamics.
Remuzzi
A
A
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Schieppati
A
A
Battaglia
C
C
Remuzzi
G
G
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D003911:Dextrans / Q000097:blood / Q000652:urine; D004656:Enalapril / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate; D006801:Humans; D006978:Hypertension, Renovascular / Q000150:complications*; D007008:Hypokalemia / Q000150:complications / Q000503:physiopathology; D007010:Hyponatremia / Q000150:complications* / Q000503:physiopathology; D007444:Inulin / Q000097:blood / Q000652:urine; D007678:Kidney Glomerulus / Q000503:physiopathology*; D008297:Male; D011507:Proteinuria / Q000188:drug therapy* / Q000209:etiology; D010130:p-Aminohippuric Acid / Q000097:blood / Q000652:urine
D000806:Angiotensin-Converting Enzyme Inhibitors; D003911:Dextrans; D004656:Enalapril; D007444:Inulin; D010130:p-Aminohippuric Acid