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 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 microIU/ml) and post-load (20+/-4 microIU/ml) insulin levels, and salt sensitivity. Going from a high-sodium ( approximately 300 mmol) to a low-sodium diet ( approximately 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 ( approximately 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.
Hoffmann
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School of Pharmacy, Clinical Pharmacology Unit, Center for the Detection and Treatment of Silent Risk Factors for Cardiovascular and Metabolic Diseases, Central University of Venezuela, Caracas, Venezula.
Alfieri
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Cubeddu
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D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D031204:Caloric Restriction; D015444:Exercise / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D017673:Sodium Chloride, Dietary / Q000378:metabolism*; D014687:Venezuela
D007004:Hypoglycemic Agents; D017673:Sodium Chloride, Dietary; D009569:Nitric Oxide; D008687:Metformin