Effect of oncotic pressure on apolipoprotein A-I metabolism in the rat.
The nephrotic syndrome is characterized by reduced plasma albumin and colloid osmotic pressure (pi), urinary protein loss and hyperlipidemia. High-density lipoprotein (HDL) and the level of apo A-I, the principal apolipoprotein in HDL, is increased in nephrotic rats and rats with hereditary analbuminemia (NAR)--animals with virtually no albumin in plasma and reduced plasma pi, but without proteinuria, suggesting that urinary protein loss is not responsible for increased plasma apo A-I levels. We conducted these studies to determine the mechanism responsible for increased plasma apo A-I levels in the nephrotic syndrome and NAR and to determine whether reduced plasma pi or albumin was responsible for increased apo A-I. We first measured the clearance of 125I apo A-I HDL in NAR and rats with passive Heymann nephritis (HN) compared with normal Sprague Dawley (SD) control. Both the clearance of apo A-I and fractional apo A-I turnover rate (FTR) were significantly reduced both in HN (7.40 +/- 2.18% plasma pool/hr) and NAR (5.63 +/- 1.12) compared with SD (9.87 +/- 0.75). Total apo A-I turnover rate, which in steady state equals apo A-I synthesis rate, was also significantly increased in both HN (487 +/- 127 micrograms/100 g body weight/hr) and NAR (253 +/- 16), compared with SD (216 +/- 19). Thus decreased apo A-I catabolism and increased synthesis both contributed to increased apo A-I levels in HN and NAR. We then infused either f3p4roncotic human albumin or ficoll into two additional groups of HN for days in quantities sufficient to maintain plasma pi within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)
Kaysen
G A
GA
Department of Medicine, University of California Davis School of Medicine 95616, USA.
Hoye
E
E
Jones
H
H
van Tol
A
A
Joles
J A
JA
D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D005921:Glomerulonephritis / Q000097:blood / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009404:Nephrotic Syndrome / Q000097:blood / Q000378:metabolism; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism
D016632:Apolipoprotein A-I; D012709:Serum Albumin; D002784:Cholesterol