Effects of lifestyle changes and metformin on salt sensitivity and nitric oxide metabolism in obese salt-sensitive Hispanics

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 kgm2), waist (11.5 ± 0.5 cm), systolic blood pressure (SBP) (8.6 ± 0.41 mm Hg), diastolic blood pressure (DBP) (5.5 ± 0.4mm Hg), triglyceride (40 ± 5 mg/dl), fasting (8.3 ± 1 μ/IUml) and post-load (20 ± 4 μIU/ml) insulin levels, and salt sensitivity. Going from a high-sodium (∼300 mmol) to a low-sodium diet (∼30mmol of sodium/ day) lowered SBP/DBP by 14.7 ± 1.7/7.4 ± 0.9mm Hg at baseline and by 8.6 ± 1.9/3.2 ± 1.2mm Hg after treatment (P < 0.001). More importantly, blood pressure (BP) sensitivity to customary levels of dietary salt (̃150mmol 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 ± 0.5mm 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.