Salt Intake, Microbiota, Immune Response and Endothelial Function in Hypertension

Impact of Salt Intake on Gut Microbiota, Th17 Immune Response and Endothelial Function in Hypertensive Patients

Hypertension is a significant cardiovascular risk factor which affects 45% of the adult population. Salt intake is essential in the development and progression of hypertension. A reduction in salt intake is associated with a reduction in blood pressure and a 25% lower risk of suffering a cardiovascular event. The mechanisms involved in the association between salt intake and blood pressure are a topic of discussion. Increased salt intake can modify cardiovascular function, inducing endothelial dysfunction, modyfing the activity of the immune system and increasing inflammation or oxidative stress. In recent years, dietary salt intake has been linked to intestinal depletion of certain genera of bacteria such as Lactobacillus. Tryptophan metabolites formed by these bacteria have been shown to modulate the activity of pro-inflammatory cells such as Th17/CD4+, interleukin 17a producing cells. Studies in animal models have demonstrated that interleukin 17a is able to raise blood pressure by hindering endothelium-dependent vasodilation mechanisms. It is also able to cause sodium and water retention, increase albuminuria, induce renal microvascular injury and vasoconstriction and promote vascular stiffening, cardiac hypertrophy and fibrosis. The main objective of this trial is to describe the relationship between salt intake, gut commensal microbiota, Th17 activity, endothelial dysfunction and blood pressure evolution in a sample of patients with essential hypertension.

Trial participants, care providers and study investigators will be blinded to assigned interventions.

Low salt diet, aiming at a daily sodium intake of 50 mmol plus oral salt supplements (9 grams) to achieve an overall daily sodium intake of 200 mmol.

Low salt diet, aiming at a daily sodium intake of 50 mmol plus oral placebo supplements to achieve an overall daily sodium intake of 50 mmol.

Taxonomic metagenomic analysis, analyzing the composition at the level of family, genus and species. Percentage of variation of each species in each control.

Percentage of change in total body water, total intracellular water, total extracellular water, fat mass, percentage of fat, lean mass, and muscle-skeletal mass.

Inclusion Criteria: Age ≥18 years. Diagnosis of primary hypertension on treatment for at least 12 months with an ACEI or ARB-II in monotherapy. Able to understand the study objectives and to provide written informed consent. Exclusion Criteria: Severe hypertension, defined as a sitting systolic blood pressure ≥200 mmHg, a sitting diastolic blood pressure ≥115 mmHg or a maximum-minimum difference of ≥20 mmHg in systolic blood pressure or ≥10 mmHg in diastolic blood pressure between the right and left arms after three measurements on each arm. Suggestive symptoms of secondary hypertension, such as abrupt onset hypertension, age <30 years, advanced end organ damage, new-onset diastolic hypertension in the elderly, Treated with antihypertensive drugs other than ACEIs or ARBs. Use of drugs that affect diuresis or natriuresis. Poorly controlled type 1 or 2 diabetes, defined as a fasting blood glucose ≥200 mg/dl or HbA1c ≥9%. History of cardiovascular disease, defined as acute myocardial infarction, ischemic transient attack or stroke, congestive heart failure, peripheral vascular disease or cardiac arrhythmias. Chronic obstructive pulmonary disease. Liver or kidney disease. Pregnant or lactating women. Legal incapacity or impossibility to understand the study objectives.