Reduced susceptibility to oxidation of low-density lipoprotein in patients with overproduction of nitric oxide (Bartter's and Gitelman's syndrome)

Background The oxidation of low-density lipoprotein (LDL) might play an important role in the development of atherosclerosis. Objective To establish whether greater than normal production of nitric oxide (NO) in vivo protects LDL from oxidation, Patients and methods We studied nine subjects affected by Bartter's and Gitelman's syndrome (both characterized by greater than normal production of NO), and 10 subjects matched for age, sex and lipid levels as controls, LDL particles were isolated from plasma by density gradient ultracentrifugation. Susceptibility of LDL to oxidation was evaluated after incubation with copper sulfate solution, by measuring the formation of conjugated dienes, the thiobarbituric acid-reactive substances, and the volatile peroxidation products of n-3 (propanal) and n-6 (pentanal and hexanal) polyunsaturated fatty acids. Phospholipid fatty acid composition of LDL was determined by gas chromatography. LDL alpha-tocopherol concentrations were measured. Results Patients with Bartter's and Gitelman's syndrome had LDL particles smaller and/or denser than those of controls [R-f = 0.38 +/- 0.03 versus 0.42 +/- 0.02 (mean +/- SD), P< 0.01], which hence were assumed to be more oxidizable, The phospholipid fatty acid composition of LDL and the alpha-tocopherol concentrations did not significantly differ between patients and controls, The duration of the lag phase, which is the time preceding formation of conjugated dienes, did not differ between groups, but the lag phase times were related to urinary excretion of nitrite/nitrate from patients (r = 0.66, P< 0.05), Moreover, patient LDL had produced less thiobarbituric acid-reactive substances after 5 h (P< 0.04), and less pentanal and hexanal after 5 and 6 h (P< 0.04 and P< 0.02, respectively) than had that of controls, Conclusions Greater than normal production of NO in vivo is associated with lower than normal susceptibility of LDL to oxidation in vitro, suggesting that NO plays a protective role in the development of atherosclerosis, I Hypertens 16:1001-1008 (C) 1998 Lippincott-Raven Publishers.