REDUCED SUSCEPTIBILITY TO OXIDATION OF LOW-DENSITY-LIPOPROTEIN IN PATIENTS WITH OVERPRODUCTION OF NITRIC-OXIDE (BARTTERS AND GITELMANS-SYNDROME)

Background The oxidation of low-density lipoprotein (LDL) might play a n important role in the development of atherosclerosis. Objective To e stablish whether greater than normal production of nitric oxide (NO) i n vivo protects LDL from oxidation, Patients and methods We studied ni ne subjects affected by Bartter's and Gitelman's syndrome (both charac terized by greater than normal production of NO), and 10 subjects matc hed for age, sex and lipid levels as controls, LDL particles were isol ated from plasma by density gradient ultracentrifugation. Susceptibili ty of LDL to oxidation was evaluated after incubation with copper sulf ate solution, by measuring the formation of conjugated dienes, the thi obarbituric acid-reactive substances, and the volatile peroxidation pr oducts of n-3 (propanal) and n-6 (pentanal and hexanal) polyunsaturate d fatty acids. Phospholipid fatty acid composition of LDL was determin ed by gas chromatography. LDL alpha-tocopherol concentrations were mea sured. 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, w hich is the time preceding formation of conjugated dienes, did not dif fer between groups, but the lag phase times were related to urinary ex cretion of nitrite/nitrate from patients (r = 0.66, P< 0.05), Moreover , patient LDL had produced less thiobarbituric acid-reactive substance s 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, Conclusi ons Greater than normal production of NO in vivo is associated with lo wer than normal susceptibility of LDL to oxidation in vitro, suggestin g that NO plays a protective role in the development of atherosclerosi s, I Hypertens 16:1001-1008 (C) 1998 Lippincott-Raven Publishers.