Effect of an Isolevuglandin Scavenger on Salt Sensitivity of Blood Pressure and Immune Cell Activation in Humans

Prior treatment

• Acute cardiovascular event(s) within the previous 6 months,
• Current excessive alcohol or illicit drug use,
• BP below the inclusion criteria levels after discontinuation of therapy,
• Concomitant diabetes mellitus, type I or II,
• Treatment with agents known to increase BP (e.g., adrenergic agonists for ADHD, SSRI and SNRI antidepressants, chronic use of decongestants or non-steroidal anti-inflammatory drugs,
• Use of glucocorticoids, immunosuppressants, direct immunomodulators or chemotherapeutic drugs that in the judgment of the investigators may include a major inflammatory component,
• Use of monoamine oxidase inhibitors (MAO-I),
• Use of nitrate therapy. (Participants who are taking PDE-5 inhibitors will be instructed to discontinue use at least 48 hours prior to testing),
• Patients with resistant hypertension, defined as above-goal blood pressure despite the concurrent use of three antihypertensive drug classes at screening, will be excluded for safety reasons,
• Use of drugs such as anticoagulants (e.g., warfarin), beta-blockers, antiarrhythmics, antidepressants/antipsychotics, and other medications primarily metabolized by CYP2C9, CYP2C19, and CYP2D6 that may cause drug-drug interaction.

Other illness

• Autoimmune disease,
• Confirmed or suspected renal, renovascular or endocrine causes of secondary hypertension,
• Active or ongoing infection, including HIV/AIDS,
• Active or ongoing malignancy with the exception of basal cell carcinoma of the skin,
• Severe psychiatric disorders,
• Any condition that may alter the immunological results of the study including rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, giant cell arteritis, psoriasis, inflammatory bowel disease, and multiple sclerosis,
• Individuals who have contraindications to high salt diets (e.g. heart, renal, or liver failure) or low salt diets (e.g. postural orthostatic tachycardia syndrome, prescribed salt tablets, fludrocortisone or midodrine) or 24-hr ambulatory blood pressure monitoring (e.g. women with bilateral upper extremity lymphedema following breast cancer surgeries),

Lab values

• Prior diagnosis of liver cirrhosis or the following abnormal liver function studies: AST or ALT \>1.5x the upper limit of normal or total bilirubin ≥1.5 mg/dl,

Age

• Younger or older than inclusion criteria,

Other

• Salt-resistant people,
• inability to understand the nature, scope, and possible consequences of the study or to participate in/comply with the protocol,
• Recent vaccination,
• Pregnant or breastfeeding
• Women of childbearing potential unwilling to use highly effective contraceptive (see Risk section),
• Use of Aspirin,
• Individuals with medical contraindications to certain food content,
• Average of three office-based blood pressure readings greater than 160 mmHg systolic or 100 mmHg diastolic will not be eligible for enrollment,

• We will perform analyses in participants previously phenotyped for SSBP, defined as a change in systolic blood pressure ≥10 mmHg from salt-loading to salt-depletion,
• Over 18 years of age. Able to give informed consent,