Whether atrial natriuretic hormone (ANH) has biological effects at physiological plasma levels in man is not known. Accordingly, we investigated the effects of a 3-h low dose infusion of human ANF (0.75 pmol/kg.min; i.e. 0.0023 micrograms/kg.min) in six normal men, whose sodium intake was normal while sitting, in a single blind, random order, placebo-controlled study. The ANF infusions induced changes in plasma ANH concentrations entirely within the range for normal subjects. The small increases in plasma ANH values were associated with a significant rise in urinary excretion of sodium, magnesium, calcium, and cGMP. PRA and plasma aldosterone concentrations uniformly decreased to 50% and 64% of placebo values, respectively. Systolic and mean arterial pressures fell significantly from preinfusion values during the ANH infusions. These findings constitute strong evidence that ANH is a hormone of physiological significance in the regulation of body fluid volumes in normal man.

Apolipoprotein (apo) E is a 34.2 kDa glycoprotein synthesized by the liver and to a lesser extent by peripheral tissues ( 1 ). It is associated in plasma with triglyceride-rich lipoproteins (TRL) and HDL particles ( 2 ). ApoE plays a central role in mediating hepatic recognition and uptake of TRL and their remnants by acting as a ligand for lipoprotein binding to the LDL receptor, LDL receptorrelated protein, and glycosaminoglycans ( 3 ). ApoE may also activate enzymes involved in lipoprotein metabolism, including hepatic lipases, cholesteryl ester transfer protein, and lecithin cholesteryl:acytransferase ( 4 ). The apoE gene is polymorphic, with three common alleles coding for three major isoforms identifi ed as E2, E3, and E4 ( 5 ).Type III hyperlipidemia, also known as dysbetalipoproteinemia, is a rare form of genetic dyslipidemia characterized by elevated plasma cholesterol and triglycerides and the presence of cholesterol-enriched remnant particles, collectively known as ␤ -VLDL ( 6 ). The accumulation of ␤ -VLDL particles may be associated with impaired TRL catabolism ( 7 ). Type III hyperlipidemic subjects may have severe xanthomatosis and signifi cantly increased risk of developing premature atherosclerosis ( 8 ). The majority of type III hyperlipidemic subjects are homozygotes for the apoE2 allele of the apoE ( APOE ) gene. However, <10% of apoE2 homozygotes develop hyperlipidemia, and most apoE2/E2 subjects are either normolipidemic or hypocholesterolemic ( 6 ). The onset of hyperlipidemia may be associated with additional genetic factors and/or environmental factors such as obesity, diabetes, and menopausal status ( 6 ). The regulation of lipoprotein transport in subjects with the apoE2/E2 genotype, in particular those withAbstract The effect of apolipoprotein (apo) E genotype on apoB-100 metabolism was examined in three normolipidemic apoE2/E2, fi ve type III hyperlipidemic apoE2/E2, and fi ve hyperlipidemic apoE3/E2 subjects using simultaneous administration of 131 I-VLDL and 125 I-LDL, and multicompartmental modeling. Compared with normolipidemic apoE2/E2 subjects, type III hyperlipidemic E2/E2 subjects had increased plasma and VLDL cholesterol, plasma and VLDL triglycerides, and VLDL and intermediate density lipoprotein (IDL) apoB concentrations ( P < 0.05). These abnormalities were chiefl y a consequence of decreased VLDL and IDL apoB fractional catabolic rate (FCR). Compared with hyperlipidemic E3/E2 subjects, type III hyperlipidemic E2/E2 subjects had increased IDL apoB concentration and decreased conversion of IDL to LDL particles ( P < 0.05). In a pooled analysis, VLDL cholesterol was positively associated with VLDL and IDL apoB concentrations and the proportion of VLDL apoB in the slowly turning over VLDL pool, and was negatively associated with VLDL apoB FCR after adjusting for subject group. VLDL triglyceride was positively associated with VLDL apoB concentration and VLDL and IDL apoB production rates after adjusting for subject group. A defective apoE contributes to altered lipoprotein me...

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We have studied the influence of triglyceride-rich particles on the analytical bias of apolipoprotein B measurements by various immunoturbidimetric methods. Three commercially available methods grossly overestimate apolipoprotein B in samples with even moderately above-normal triglyceride concentrations. This effect is due to the increased relative reactivity of very-low-density lipoproteins in these reagent systems, and can be eliminated by including Tween 20 (2 g/L) in the reagent buffer. We have developed, and describe, an automated immunoturbidimetric method that allows the accurate determination of apolipoprotein B in the plasma of patients with hypertriglyceridemia.

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