BackgroundThe oxidation of low-density lipoprotein (LDL) might play an important role in the development of atherosclerosis.ObjectiveTo establish whether greater than normal production of nitric oxide (NO)in vivoprotects LDL from oxidation.Patients and methodsWe 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 α-tocopherol concentrations were measured.ResultsPatients with Bartter's and Gitelman's syndrome had LDL particles smaller and/or denser than those of controls [Rf= 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 α-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 6h (P< 0.04 andP< 0.02, respectively) than had that of controls.ConclusionsGreater than normal production of NOin vivois associated with lower than normal susceptibility of LDL to oxidationin vitro, suggesting that NO plays a protective role in the development of atherosclerosis.