RTN-001 for Uncontrolled Hypertension

Inclusion Criteria: * Male or female patients age 18 to 75 years, inclusive, at the Screening Visit. * Uncontrolled HTN despite being on a stable regimen of 2-5 antihypertensive medications. * Mean BP of ≥135/80 mm Hg. * Body mass index of 18 to 35 kg/m2. Exclusion Criteria: * Mean seated SBP \>175 mm Hg and/or DBP \>110 mm Hg. * Current or planned use of nitrates and/or alpha-blockers or other drugs known to affect BP during the study period. * Participants who use PDE5 inhibitors for other indications that cannot or will not refrain from use of PDE5 inhibitors for 7 days before and during their entire period of participation in the study. * History of hypotension, fainting spells, blackouts or autonomic dysfunction, including orthostatic hypotension. * Known diagnosis of secondary hypertension (e.g. Cushing's Disease or hyperaldosteronism, renal fibrodysplasia, renal artery stenosis, etc., clinically significant aortic stenosis etc.). * Recent (within 3 months before the Screening Visit \[Visit S1\]) myocardial infarction; unstable angina leading to hospitalization; uncontrolled, symptomatic atrial fibrillation, or any cardiac arrhythmia that has not been clinically stable for at least 3 months prior to screening. Participants with implantable pacemakers or automatic implantable cardioverter defibrillators may be considered if deemed by the Investigator to be stable for the previous 3 months. * Uncontrolled hypothyroidism * Liver disease or dysfunction * Renal dysfunction (\<45 mL/min/1.73m²) or glomerulonephritis * Active infection or major illness * Gastrointestinal conditions or procedures (including weight loss surgery \[eg, Lap-Band or gastric bypass\]) that may affect drug absorption. * Hematologic or coagulation disorders * Active malignancy * Unexplained creatine kinase (CK) \>3 × ULN at any time before randomization * A known history of temporary or permanent partial or total vision loss * A known history of "crowded" optic disc. * A known history of retinitis pigmentosa, a rare genetic eye disease. * Any prescription or over-the counter drugs or herbal supplements known to be strong inhibitors of CYP3A4 enzymes * NHYA class III-IV symptoms of heart failure. * History of diabetes or suspected diabetes with glycosylated hemoglobin \> 10% or fasting glucose \>250 mg/dl at Screening Visit (S1).