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

Abstract

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 saltsensitive 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 (9.870.3 kg), body mass index (3.970.2 kg/m 2 ), waist (11.570.5 cm), systolic blood pressure (SBP) (8.670.4 mm Hg), diastolic blood pressure (DBP) (5.570.4 mm Hg), triglyceride (4075 mg/dl), fasting (8.371 lIU/ml) and post-load (2074 lIU/ml) insulin levels, and salt sensitivity. Going from a highsodium (B300 mmol) to a low-sodium diet (B30 mmol of sodium/day) lowered SBP/DBP by 14.771.7/7.470.9 mm Hg at baseline and by 8.671.9/3.271.2 mm Hg after treatment (Po0.001). More importantly, blood pressure (BP) sensitivity to customary levels of dietary salt (B150 mmol of sodium/day) was abolished by the lifestyle-metformin treatment. Differences in SBP/DBP between usual and low salt averaged 1171/871 mm Hg before treatment, and 371/170.5 mm Hg after treatment (Po0.001). 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 lifestylemetformin treatment.

Salt sensitivity: a review with a focus on non-Hispanic blacks and Hispanics

“…After obtaining baseline values including weight and BP on low- and high-salt diets, subjects were put on a lifestyle program with a goal of weight reduction, and prescribed Metformin, titrated up to 500 mg three times a day. 70 This intervention achieved a significant reduction in subject’s weight by 13%, reductions in systolic and diastolic BP, and most notably, reduced the sensitivity of the participant’s BP to salt intake by about 40%. Researchers also measured urinary excretion of NO metabolites.…”

Enhancement of Neural Salty Preference in Obesity

“…Furthermore, overweight and obese individuals are prone to consume more dietary salt, and their BMI are correlated with increased salt intake [1, 2]. In addition, high salt intake increasing blood pressure has been shown in obese subjects, and modification of salt sensitivity through therapeutic weight reduction can lower blood pressure [3, 4]. However, the underlying mechanisms on obesity related high salt intake remain elusive.…”

Salt-induced hemodynamic regulation mediated by nitric oxide

“…From studies on salt-sensitive individuals, Cubeddu et al [12] also provided evidence suggesting that salt sensitivity appears to be determined by an inability to increase or to sustain nitric oxide production in response to high salt; insufficient nitric oxide production during high-salt intake may in turn lead to an altered pressure-natriuresis relationship and to an increase in blood pressure. In healthy obese salt-sensitive individuals, nitric oxide metabolite excretion was inhibited during high-salt ingestion, and this impairment was corrected by the lifestyle-metformin treatment, suggesting that restoration of the inability to increase or sustain nitric oxide production in response to high salt may account for the correction of salt sensitivity induced by the lifestyle-metformin treatment [13].…”