Background-The basis for progressive attenuation of the effects of organic nitrates during long-term therapy (nitrate tolerance) remains controversial; proposed mechanisms include impaired nitrate bioconversion resulting in decreased release of nitric oxide (NO) from nitrates and/or increased NO clearance through a reaction with incrementally generated superoxide (O 2 -). Methods and Results-Patients undergoing elective coronary artery bypass were randomized to receive 24 hours of intravenously infused nitroglycerin (NTG; nitrate group) or no nitrate therapy (control group). Discarded segments of the internal mammary artery and saphenous vein were used to examine (1) vascular responsiveness to NTG, sodium nitroprusside, and the calcium ionophore A23187; (2) bioconversion of NTG to 1,2-and 1,3-glyceryl dinitrate; and (3) the generation of O 2 -. Responses to NTG were reduced 3-to 5-fold in vessels from the nitrate group compared with control vessels (PϽ0.01 for both types of segments), whereas responses to sodium nitroprusside and A23187 were unchanged. Tissue content of 1,2-glyceryl dinitrate was lower (Pϭ0.012) in the saphenous veins from the nitrate group than in those from the control group. O 2 -generation was greater (PϽ0.01) in internal mammary artery samples from the nitrate group than in those from the control group. However, incremental O 2 -generation induced by an inhibitor of superoxide dismutase did not affect NTG responses. Conclusions-NTG tolerance in patients with coronary artery disease is nitrate-specific and is associated with evidence of impaired NTG bioconversion. Tolerance was associated with incremental O 2 -generation, but short-term elevation of O 2

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The self-reported prevalence of, and attitudes to and perceptions of, osteoporosis in the South Australian community were assessed using data collected as part of the 1995 South Australian Health Omnibus Survey (household interviews)--a clustered, self-weighting, multistage sample of households in metropolitan and country centers. The self-reported prevalence was 4.8 (95% CI: 3.7-5.8) and 1.4% (95% CI: 0.8-2.0) for women (n = 1531) and men (n = 1485) respectively. For individuals with osteoporosis, calcium was the favored treatment (52%), while 33% of women were on hormone replacement therapy. An appropriate definition of osteoporosis was given by 62% of women and 37% of men. The main risk factors were reported as lack of calcium and age. There was a significant association between knowledge of the definition of osteoporosis and identification of correct risk factors. A high perceived risk of osteoporosis was reported in 23% of women and 7% of men. Osteoporosis risk was assessed as higher in those who did not adopt recognized prevention measures. Perception of risk was not related to the individual's own risk factors. Self-reported prevalence of osteoporosis significantly underestimates the likely true prevalence and general awareness and knowledge is much lower for men than women. The importance of individual risk factors for osteoporosis are not understood by the general community.