Salt sensitivity is associated with obesity, and increased cardiovascular morbidity and mortality. We investigated whether treatment of obesity and its associated metabolic abnormalities corrects salt sensitivity and restores impaired nitric oxide ( NO) metabolism characteristic of salt sensitivity. Twenty, otherwise, healthy obese salt-sensitive subjects completed a 12-month program of caloric restriction, aerobic exercise and metformin. Two salt sensitivity tests were performed, that is at baseline and end of program. Lifestyle-metformin treatment decreased weight (9.8 +/- 0.3 kg), body mass index (3.9 +/- 0.2 kg/m(2)), waist (11.5 +/- 0.5 cm), systolic blood pressure (SBP) (8.6 +/- 0.4 mm Hg), diastolic blood pressure (DBP) (5.5 +/- 0.4 mm Hg), triglyceride (40 +/- 5 mg/dl), fasting (8.3 +/- 1 mu IU/ml) and post-load (20 +/- 4 mu IU/ml) insulin levels, and salt sensitivity. Going from a high-sodium (similar to 300 mmol) to a low-sodium diet (similar to 30 mmol of sodium/day) lowered SBP/DBP by 14.7 +/- 1.7/7.4 +/- 0.9 mm Hg at baseline and by 8.6 +/- 1.9/3.2 +/- 1.2 mm Hg after treatment (P < 0.001). More importantly, blood pressure (BP) sensitivity to customary levels of dietary salt (similar to 150 mmol of sodium/day) was abolished by the lifestyle-metformin treatment. Differences in SBP/DBP between usual and low salt averaged 11 +/- 1/8 +/- 1 mm Hg before treatment, and 3 +/- 1/1 +/- 0.5 mm Hg after treatment (P < 0.001). At baseline, NO-metabolite excretion was inhibited during high salt; this impairment was corrected by the lifestyle-metformin treatment. In conclusion, acquired correctable factors play an important role in the pathogenesis of salt sensitivity associated with obesity. Correction of salt sensitivity may account for the BP lowering induced by weight reduction. Restoration of the inability to increase or sustain NO production in response to high salt could account for the correction of salt sensitivity induced by the lifestyle-metformin treatment.
