The patient has uncontrolled or poorly controlled hypertension despite standard medical management as defined in this protocolXx_NEWLINE_xXNo history of grade 4 hypertension, defined as hypertension resulting in life-threatening consequences (e.g., malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis)Xx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXUncontrolled chronic hypertension defined as systolic > 150 or diastolic > 90 despite optimal therapy.Xx_NEWLINE_xXPatients with uncontrolled hypertension (>= 140/90 mmHg) are NOT eligible for participationXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXPatients with poorly controlled hypertension on multiple antihypertensivesXx_NEWLINE_xXNeed for > 2 antihypertensive medications for management of hypertension (including diuretics).Xx_NEWLINE_xXUncontrolled hypertension (as defined as ? 160/90 despite optimal medical management)Xx_NEWLINE_xXUncontrolled arterial hypertension >/= 150/ >/= 90 millimeter of mercury (mmHg) despite standard medical management;Xx_NEWLINE_xXPatients with uncontrolled hypertension; patients with a history of hypertension must be well controlled (< 160/90) on a regimen of hypertensive medicationXx_NEWLINE_xXPoorly controlled hypertension. During screening ?2/3 of readings must be < 160/90, regardless of whether on a regimen of anti-hypertensive therapy or not.Xx_NEWLINE_xXHistory of significant cardiac disease or uncontrolled hypertensionXx_NEWLINE_xXUncontrolled hypertension or diabetesXx_NEWLINE_xXUncontrolled hypertension or uncontrolled diabetes within 14 days prior cycle 1, day 1Xx_NEWLINE_xXPatients with uncontrolled hypertension (> 140/90 mmHg) are NOT eligible for participationXx_NEWLINE_xXUncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertensionXx_NEWLINE_xXUncontrolled hypertension or diabetesXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXOther concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration)Xx_NEWLINE_xXPoorly controlled hypertension despite anti-hypertensive medicationsXx_NEWLINE_xXA past medical history of other clinically significant cardiovascular disease (eg, uncontrolled hypertension, history of labile hypertension, history of poor compliance with an antihypertensive regimen).Xx_NEWLINE_xXSubjects with other uncontrolled medical conditions, e.g. myocardial infarction, cerebrovascular accident, diabetes or hypertension.Xx_NEWLINE_xXNeed for > 2 antihypertensive medications for management of hypertension (including diuretics).Xx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXPulmonary hypertensionXx_NEWLINE_xXHas uncontrolled or poorly controlled hypertensionXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXUncontrolled hypertension despite optimal medical managementXx_NEWLINE_xXUncontrolled hypertension (despite medical therapy); blood pressure should be < 140/90 in accordance with American Heart Association definition of hypertensionXx_NEWLINE_xXUncontrolled hypertension (> 150/100 mmHg)Xx_NEWLINE_xXHave uncontrolled diabetes or have hypertension requiring more than 3 medications for control of hypertension.Xx_NEWLINE_xXNo uncontrolled intercurrent illness including active infection, uncontrolled diabetes, uncontrolled hypertension, or uncontrolled psychiatric illness which in the investigator’s opinion would limit compliance with study requirements or compromise patient safetyXx_NEWLINE_xXPatients must not have uncontrolled hypertensionXx_NEWLINE_xXUncontrolled hypertension or diabetesXx_NEWLINE_xXUncontrolled hypertension (HTN)Xx_NEWLINE_xXUncontrolled hypertension (above 150/95 mm Hg)Xx_NEWLINE_xXSevere pulmonary hypertension (PHT) (on echo or right side cardiac catheterization);Xx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXPoorly controlled hypertension, defined as sustained, uncontrolled, non-episodic baseline hypertension consistently above 159/99 mmHg despite optimal medical managementXx_NEWLINE_xXPatients with uncontrolled hypertensionXx_NEWLINE_xXUncontrolled hydropericardiumXx_NEWLINE_xXSustained uncontrolled hypertension (> 150/90 average over 1 week) despite optimal medical managementXx_NEWLINE_xXHypertension that is unstable or not controlled by medication.Xx_NEWLINE_xXPatient has poorly controlled hypertension and on multiple antihypertensivesXx_NEWLINE_xXAny known uncontrolled cardiovascular disease, pulmonary embolism, hypertension not adequately controlled by standard medications within 3 months prior to enrollment.Xx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXUncontrolled diabetes or hypertensionXx_NEWLINE_xXPatients with uncontrolled hypertensionXx_NEWLINE_xXPatients with uncontrolled hypertension (HTN) (> 160/90) will not be admitted onto the studyXx_NEWLINE_xXFOR ALL PHASES (Ib AND II): Uncontrolled arterial hypertension despite optimal medical managementXx_NEWLINE_xXSevere pulmonary hypertension (PHT) (on echo or right side cardiac catheterization)Xx_NEWLINE_xXCriteria for hypertension: Blood pressure greater than 170/90 or 2 standard deviations (SD) from normal based on age and weight nomogram on 3 separate measurements; uncontrolled hypertension (HTN)Xx_NEWLINE_xXPatients at risk of brain perfusion problems, e.g., carotid stenosis • Uncontrolled hypertension requiring clinical interventionXx_NEWLINE_xXPatients must not have symptomatic hypertensionXx_NEWLINE_xXOther concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal [GI] tract ulceration)Xx_NEWLINE_xXPulmonary hypertension.Xx_NEWLINE_xXHypertension requiring 3 or more anti-hypertensive medications to controlXx_NEWLINE_xXSevere or unstable cardiovascular disease or uncontrolled hypertensionXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXUncontrolled or severe hypertension, or cerebrovascular disease.Xx_NEWLINE_xXHave uncontrolled hypertension; subjects with a history of hypertension are permitted in the study provided their blood pressure is controlled by anti-hypertensive therapyXx_NEWLINE_xXPatients with diagnosed uncontrolled hypertension (> 150/90 mmHg) are to be excludedXx_NEWLINE_xXPatients with hypertension controlled with medications are allowedXx_NEWLINE_xXUncontrolled hypertension or uncontrolled diabetes within 14 days prior to start of treatmentXx_NEWLINE_xXThe patient has uncontrolled or poorly-controlled hypertension (>= 150 / >= 90 mm Hg) despite standard medical managementXx_NEWLINE_xXuse of systemic steroids or immunosuppressive medication Pulmonary hypertension will not be an exclusion criterion as patients with pulmonary hypertension were shown to have higher bursting pressures following PA sealing in previous studies.Xx_NEWLINE_xXUncontrolled hypertension (refer to World Health Organization [WHO]-International Society of Hypertension [ISH] guidelines)Xx_NEWLINE_xXUncontrolled hypertension despite optimal medical management (per investigator´s assessment)Xx_NEWLINE_xXUncontrolled intercurrent illness, condition, or circumstances that could limit compliance with the study, including, but not limited to the following: acute or chronic graft versus host disease, uncontrolled diabetes mellitus or hypertension, or psychiatric conditionsXx_NEWLINE_xXUncontrolled hypertension defined as > 140/90 and not cleared for surgery at the time of consentXx_NEWLINE_xXPatients with extrahepatic disease, portal hypertension, or bilobar disease are allowedXx_NEWLINE_xXUncontrolled diabetes or hypertensionXx_NEWLINE_xXSubjects with a history of pulmonary hypertension is excludedXx_NEWLINE_xXPoorly controlled hypertension despite multiple antihypertensive medication orXx_NEWLINE_xXUncontrolled hypertension, uncontrolled pulmonary hypertension or uncontrolled diabetes within 14 days prior to enrollmentXx_NEWLINE_xXHistory of central serous retinopathy (CSR) or retinal vein occlusion (RVO), or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)Xx_NEWLINE_xXUncontrolled diabetes, hypertension or other medical conditions that may interfere with assessment of toxicityXx_NEWLINE_xXAny ophthalmopathy visible at screening that would be considered a risk factor for CSR or RVO by the ophthalmologist (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, history of hyperviscosity or hypercoagulability syndromes)Xx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXUncontrolled hypertension or uncontrolled diabetesXx_NEWLINE_xXUncontrolled arterial hypertension despite appropriate medical therapyXx_NEWLINE_xXHave uncontrolled severe hypertensionXx_NEWLINE_xXMust not have any uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment.Xx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXAny ophthalmopathy visible at screening that would be considered a risk factor for CSR or RVO by the ophthalmologist (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, history of hyperviscosity or hypercoagulability syndromes)Xx_NEWLINE_xXDONOR: Current uncontrolled hypertensionXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXHave a known history of uncontrolled hypertension. Patients with hypertension should be under treatment on study entry to control blood pressure.Xx_NEWLINE_xXPatients with >= grade 2 uncontrolled hypertensionXx_NEWLINE_xXPatient with poorly controlled hypertension despite multiple antihypertensivesXx_NEWLINE_xXPulmonary hypertension moderate to severe by echocardiographic standardsXx_NEWLINE_xXUncontrolled arterial hypertension despite optimal medical management (per institutional guidelines).Xx_NEWLINE_xXUncontrolled hypertension or unstable angina.Xx_NEWLINE_xXUncontrolled hypertension during screeningXx_NEWLINE_xXSevere or uncontrolled systemic diseases including uncontrolled hypertension, active bleeding diathesesXx_NEWLINE_xXUncontrolled hypertension or uncontrolled diabetes within 14 days prior to randomizationXx_NEWLINE_xXPatients who exhibit uncontrolled hypertension (>= 140/90 mmHg) or uncontrolled diabetes within 14 days prior to registration are NOT eligible for participationXx_NEWLINE_xXCurrent uncontrolled hypertensionXx_NEWLINE_xXUncontrolled arterial hypertension despite appropriate medical therapyXx_NEWLINE_xXPart 2: tachycardia and/or uncontrolled hypertensionXx_NEWLINE_xXUncontrolled hypertension at study entry; patients with a history of uncontrolled hypertension are allowed provided blood pressure is controlled by antihypertensive treatmentXx_NEWLINE_xXUncontrolled, severe concomitant comorbidity (e.g. uncontrolled hypertension, uncontrolled diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)Xx_NEWLINE_xXAny severe or uncontrolled medical condition or other condition that could affect participation in this study, including but not limited to: unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, uncontrolled hypertension, or myocardial infarction ? 6 months prior to study entryXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXUncontrolled diabetes, heart disease, hypertensionXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXUncontrolled hypertension or diabetes.Xx_NEWLINE_xXUncontrolled hypertension, major bleeding, HIV infection, or recent acute\n             cardiovascular eventXx_NEWLINE_xXA past medical history of other clinically significant cardiovascular disease - e.g., uncontrolled hypertension, history of labile hypertension or history of poor compliance with an antihypertensive regimenXx_NEWLINE_xXHistory of pulmonary hypertensionXx_NEWLINE_xXUncontrolled hypertension or uncontrolled diabetes mellitusXx_NEWLINE_xXPulmonary hypertensionXx_NEWLINE_xXUncontrolled hypertension (> 150/90 mmHg)Xx_NEWLINE_xXHypertension not adequately controlled by 3 or less medicationsXx_NEWLINE_xXHypertension not adequately controlled by 3 or less medicationsXx_NEWLINE_xXPoorly controlled hypertension despite anti-hypertensive medicationsXx_NEWLINE_xXThe participant has uncontrolled hypertension, despite antihypertensive intervention.Xx_NEWLINE_xXHistory of uncontrolled intercurrent illness including hypertension, active infection, diabetesXx_NEWLINE_xXUncontrolled hypertension defined as > 140/90 and not cleared for surgery at the time of consentXx_NEWLINE_xXCirrhosis or portal hypertensionXx_NEWLINE_xXUncontrolled hypertension (> 150/100 mmHg despite optimal medical therapy)Xx_NEWLINE_xXNYHA Class III or IV, uncontrolled hypertension, or clinically significant arrhythmiaXx_NEWLINE_xXUncontrolled diabetes or uncontrolled hypertension within 14 days prior to first doseXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXUnstable angina pectoris, uncontrolled hypertension, uncontrolled asthma or other pulmonary diseaseXx_NEWLINE_xXUncontrolled hypertension.Xx_NEWLINE_xXPoorly controlled hypertensionXx_NEWLINE_xXPatients must not have a diagnosis of uncontrolled seizure or uncontrolled hypertensionXx_NEWLINE_xXHave uncontrolled hypertension.Xx_NEWLINE_xXAny other serious cardiac illness or medical conditions such as unstable angina, pulmonary embolism, or uncontrolled hypertension.Xx_NEWLINE_xXAny other serious cardiac illness or medical conditions such as unstable angina, pulmonary embolism, or uncontrolled hypertensionXx_NEWLINE_xXSubject has history (within previous 5 years) of clinically significant pulmonary hypertension, uncontrolled systemic hypertension, hypertensive crisis, congestive heart failure, myocardial infarction, aneurysm or aneurysm repair or the left ventricular ejection fraction (LVEF) less than or equal to 50%.Xx_NEWLINE_xXPatients with poorly controlled hypertension and on multiple antihypertensivesXx_NEWLINE_xXuncontrolled cardiovascular disease or uncontrolled hypertensionXx_NEWLINE_xXhave uncontrolled hypertensionXx_NEWLINE_xXPulmonary hypertension.Xx_NEWLINE_xXHypertension defined below:Xx_NEWLINE_xXUncontrolled hypertension, or uncontrolled diabetes mellitusXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXHave uncontrolled hypertension prior to initiating study treatment, despite antihypertensive intervention.Xx_NEWLINE_xXHas prior history of uncontrolled hypertension, hypertensive crisis or hypertensive encephalopathyXx_NEWLINE_xXAny evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diathesesXx_NEWLINE_xXUncontrolled or poorly controlled hypertension.Xx_NEWLINE_xXSevere or uncontrolled systemic diseases including uncontrolled hypertensionXx_NEWLINE_xXUncontrolled symptomatic hypertension that cannot be controlled with anti-hypertensive agentsXx_NEWLINE_xXUncontrolled hypertension.Xx_NEWLINE_xXUncontrolled hypertension or diabetesXx_NEWLINE_xXUncontrolled hypertension (> 160/100 mm Hg despite optimal medical therapy)Xx_NEWLINE_xXSevere/uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant, bleeding diatheses or infectionXx_NEWLINE_xXResisted hypertensionXx_NEWLINE_xXUncontrolled hypertension or uncontrolled diabetes despite medicationXx_NEWLINE_xXUncontrolled arterial hypertension despite optimal medical management (per investigator's assessment).Xx_NEWLINE_xXHistory of hypertension not well-controlled (>= 160/90) even though on a regimen of anti-hypertensive therapyXx_NEWLINE_xXKnown history of pulmonary hypertensionXx_NEWLINE_xXControlled hypertensionXx_NEWLINE_xXSevere, uncontrolled systemic diseaseXx_NEWLINE_xXOther concurrent severe and/or uncontrolled medical disease, which could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal [GI] tract ulceration, congestive heart failure, etc.)Xx_NEWLINE_xXUncontrolled hypertension or uncontrolled diabetes within 14 days prior to the first day of treatmentXx_NEWLINE_xXUncontrolled hypertension or uncontrolled diabetes within 14 days prior to randomizationXx_NEWLINE_xXCurrent uncontrolled hypertension as well as prior history of hypertensive crisis or hypertensive encephalopathyXx_NEWLINE_xXCurrent uncontrolled hypertensionXx_NEWLINE_xXNo uncontrolled hypertension or uncontrolled diabetes (as determined by the treating physician) within 14 days prior to cycle 1 day 1Xx_NEWLINE_xXKnown history of malignant hypertensionXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXUncontrolled hypertension or diabetesXx_NEWLINE_xXUncontrolled hypertension or diabetes.Xx_NEWLINE_xXInadequately controlled arterial hypertensionXx_NEWLINE_xXUncontrolled hypertension or diabetesXx_NEWLINE_xXPulmonary hypertensionXx_NEWLINE_xXUncontrolled hypertension or uncontrolled diabetes within 14 days prior to signing consentXx_NEWLINE_xXUncontrolled arterial hypertension despite medical treatmentXx_NEWLINE_xXPatients must not have uncontrolled diabetes, uncontrolled infection despite antibiotics or uncontrolled hypertension within 30 days prior to registrationXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXUncontrolled hypertension or diabetesXx_NEWLINE_xXHistory or evidence of poorly controlled hypertensionXx_NEWLINE_xXUncontrolled arterial hypertension despite medical treatmentXx_NEWLINE_xXPatients with known pulmonary hypertensionXx_NEWLINE_xXPatients with a known history of retinal vein occlusion (RVO) or central serous retinopathy (CSR), or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyper viscosity or hypercoagulability syndromes)Xx_NEWLINE_xXPatients with severe pulmonary hypertension \r\n* Tricuspid jet velocity > 2.5 m/secXx_NEWLINE_xXPatients with uncontrolled hypertension (i.e., persistent grade 3 while undergoing treatment)Xx_NEWLINE_xXPatients with a history of hypertension must be well-controlled (< 150/90) on a regimen of anti-hypertensive therapyXx_NEWLINE_xXPatients with serious medical complications, such as serious heart disease, cerebrovascular accidents, uncontrolled diabetes mellitus, uncontrolled hypertension, pulmonary fibrosis, interstitial pneumonitis, active bleeding, an active gastrointestinal ulcer, or a serious neurological disorderXx_NEWLINE_xXPatients with uncontrolled hypertension (>= 145/90 mmHg) are NOT eligible for participationXx_NEWLINE_xXPoorly controlled hypertensionXx_NEWLINE_xXOther clinically significant heart disease (e.g. uncontrolled hypertension, or history of labile hypertension)Xx_NEWLINE_xXUncontrolled hypertension (home blood pressure readings are permitted) or prior history of hypertensive crisis or hypertensive encephalopathy; however, treatment of hypertension with medications is permittedXx_NEWLINE_xXHypertensionXx_NEWLINE_xXThe participant has uncontrolled arterial hypertension ?150 / ?90 millimeters of mercury (mm Hg) despite standard medical managementXx_NEWLINE_xXUncontrolled diabetes, hypertension or other medical conditions at the time of transition to this study that may interfere with assessment of toxicityXx_NEWLINE_xXPatient has poorly controlled hypertension and on multiple antihypertensivesXx_NEWLINE_xXUncontrolled heart failure or hypertension or uncontrolled diabetes mellitusXx_NEWLINE_xXUncontrolled heart failure or hypertension or uncontrolled diabetes mellitusXx_NEWLINE_xXOther clinically significant heart disease (i.e., Grade ?3 hypertension, history of labile hypertension, or poor compliance with an anti-hypertensive regimen)Xx_NEWLINE_xXSevere and uncontrolled disease, including:Xx_NEWLINE_xXUncontrolled hypertension or diabetesXx_NEWLINE_xXPatients with poorly controlled hypertension despite multiple antihypertensive medicationsXx_NEWLINE_xXPatients with poorly controlled hypertension despite hypertensive medicationXx_NEWLINE_xXPatients with poorly controlled hypertensionXx_NEWLINE_xXA past history of, or current uncontrolled hypertension. Blood pressure must be adequately controlled prior to dosing with VS-5584.Xx_NEWLINE_xXSubject has severe or uncontrolled systemic diseases including uncontrolled hypertension or active bleeding diatheses.Xx_NEWLINE_xXMedical conditions such as uncontrolled hypertension, uncontrolled diabetes mellitus, cardiac disease that would, in the opinion of the investigator, make this protocol unreasonably hazardousXx_NEWLINE_xXSubject has uncontrolled hypertension.Xx_NEWLINE_xXUncontrolled arterial hypertension despite optimal medical management (per investigator's assessment) (modified by amendment 1)Xx_NEWLINE_xXKnown history of malignant hypertension.Xx_NEWLINE_xXUncontrolled arterial hypertension despite medical treatmentXx_NEWLINE_xXUncontrolled hypertension despite optimal medical managementXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXUncontrolled arterial hypertension despite appropriate medical therapyXx_NEWLINE_xX12 Known history of malignant hypertension.Xx_NEWLINE_xXInadequately controlled hypertensionXx_NEWLINE_xXAny uncontrolled hypertension, arrhythmia, or active angina pectorisXx_NEWLINE_xXPatients with a history of hypertension must be well-controlled (< 150 systolic/< 100 diastolic) on a stable regimen of anti-hypertensive therapyXx_NEWLINE_xXPatients with uncontrolled intracranial hypertension syndrome (defined as: persistence of headache, transient visual obscurations, and/or diplopia despite optimal clinical management) or uncontrolled seizure activity (i.e. recorded despite optimal medical management)Xx_NEWLINE_xXUncontrolled hypertension or diabetesXx_NEWLINE_xX7. Uncontrolled congestive heart failure or uncontrolled hypertension.Xx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXHave a history of hypertensive crisis or hypertensive encephalopathy or current poorly controlled hypertension despite standard medical management.Xx_NEWLINE_xXUncontrolled seizures or uncontrolled hypertensionXx_NEWLINE_xXOther clinically significant heart disease (e.g., CHF NY Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).Xx_NEWLINE_xXHypertension uncontrolled by medicationXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXEvidence of uncontrolled bradycardia or other cardiac arrhythmia defined as ?Grade 2 according to NCI CTCAE, version 4.0, or uncontrolled hypertensionXx_NEWLINE_xXInadequately controlled hypertension or history of hypertensive crisis or encephalopathy.Xx_NEWLINE_xXKnown pulmonary hypertension of any severity.Xx_NEWLINE_xXKnown history of malignant hypertension (severe hypertension >180/120 mmHg with end organ involvement.Xx_NEWLINE_xXThe subject has a history of uncontrolled intercurrent illness including but not limited to an active infection, hypertension, or uncontrolled diabetes (e.g. glycosylated hemoglobin >= 8 percent [%]) that would limit compliance with treatment requirements.Xx_NEWLINE_xXUncontrolled hypertension (per the Investigator's discretion)Xx_NEWLINE_xXUncontrolled concurrent medical illness including uncontrolled hypertensionXx_NEWLINE_xXUncontrolled arterial hypertension despite medical treatmentXx_NEWLINE_xXUncontrolled hypertension or uncontrolled diabetes within 14 days prior to randomizationXx_NEWLINE_xXPresence of predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes), orXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXUncontrolled hypertension (per Investigator's discretion)Xx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXPatients may not be on medical therapy for hypertension at time of enrollment.Xx_NEWLINE_xXEchocardiographic evidence of pulmonary hypertension.Xx_NEWLINE_xXPoorly-controlled hypertensionXx_NEWLINE_xXUncontrolled hypertension or uncontrolled diabetes within 14 days prior to randomizationXx_NEWLINE_xXPredisposing factors to retinal vein occlusion including uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, and coagulopathy.Xx_NEWLINE_xXUncontrolled diabetes, hypertension or other medical conditions that may interfere with assessment of toxicity.Xx_NEWLINE_xXUncontrolled hypertension or cardiomyopathyXx_NEWLINE_xXHave >= Grade 2 uncontrolled hypertensionXx_NEWLINE_xXPulmonary hypertension,Xx_NEWLINE_xXKnown pulmonary hypertensionXx_NEWLINE_xXPatients with uncontrolled hypertension (systolic > 140, diastolic > 90) despite antihypertensive therapyXx_NEWLINE_xXUncontrolled arterial hypertension despite medical treatmentXx_NEWLINE_xXA history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) including:\r\n* Presence of predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes)Xx_NEWLINE_xXUncontrolled hypertension or chronic renal diseaseXx_NEWLINE_xXUncontrolled hypertension;Xx_NEWLINE_xXHave uncontrolled diabetes or have hypertension requiring more than 3 medications for control of hypertension.Xx_NEWLINE_xXHistory of hypertension that is not well-controlled (>= 160/90) on anti-hypertensive therapyXx_NEWLINE_xXUncontrolled hypertension or other uncontrolled chronic disease (e.g. diabetes mellitus, thyroid disease, pulmonary disease, etc.)Xx_NEWLINE_xXDiagnosis of pulmonary hypertensionXx_NEWLINE_xXSevere comorbidities (atrial fibrillation, pulmonary hypertension, etc...)Xx_NEWLINE_xXCurrent and past history of hypertensionXx_NEWLINE_xXKnown cardiovascular disease, uncontrolled hypertension, or new cardiac event within the past 6 monthsXx_NEWLINE_xXFor participants who are randomized in aim 1:\r\n* No uncontrolled serious medical or psychiatric condition(s) that would affect the patient’s ability to participate in the interventional study, e.g., uncontrolled hypertension, symptomatic cardiac disease, or severe/uncontrolled depression as indicated by a Patient Health Questionnaire (PHQ-9) score > 9 (Kroenke)\r\n* No diagnoses of any other invasive malignancy other than endometrial cancer or non-melanoma skin cancer which required active treatment currentlyXx_NEWLINE_xXHypertension other than mild essential hypertension controlled with medicationXx_NEWLINE_xXPatients with uncontrolled hypertension.Xx_NEWLINE_xXUncontrolled hypertension.Xx_NEWLINE_xXDiagnosis of pulmonary hypertensionXx_NEWLINE_xXSymptomatic tachycardia and uncontrolled hypertension (determined to be clinically significant by the PI)Xx_NEWLINE_xXHave tachycardia and/or uncontrolled hypertensionXx_NEWLINE_xXSymptomatic tachycardia and uncontrolled hypertension (determined to be clinically significant by the PI)Xx_NEWLINE_xXHas untreated hypertension or has hypertension under treatment that meets protocol definitions.Xx_NEWLINE_xXuncontrolled hypertensionXx_NEWLINE_xXsevere pulmonary hypertensionXx_NEWLINE_xXUncontrolled hypertension (defined as 3 consecutive readings over the past year of over 160 systolic, and over 100 diastolic)Xx_NEWLINE_xXSevere pulmonary hypertensionXx_NEWLINE_xXCONTROL (HEALTHY) GROUP: Severe pulmonary hypertensionXx_NEWLINE_xXIndividuals with a history of diabetes, hypertension, or have smoked cigarettes in the last 12 months.Xx_NEWLINE_xXMajor co-morbidities (e.g., uncontrolled diabetes, hypertension, etc.)Xx_NEWLINE_xXPatient has uncontrolled hypertensionXx_NEWLINE_xXHistory of Uncontrolled hypertensionXx_NEWLINE_xXHistory of chronic disease including diabetes, uncontrolled hypertension or thyroid diseaseXx_NEWLINE_xXSubjects with life-threatening medical conditions that would preclude bronchoscopy, including: acute cardiac failure, which is unstable despite medication use; uncontrolled hypertension; uncontrolled diabetes mellitus; or unstable coronary artery diseaseXx_NEWLINE_xXWell-controlled hypertensionXx_NEWLINE_xXUncontrolled hypertensionXx_NEWLINE_xXPatients with pulmonary hypertension or unstable cardiopulmonary conditionsXx_NEWLINE_xXKnown pulmonary hypertensionXx_NEWLINE_xXPatients with pulmonary hypertension or unstable cardiopulmonary conditionsXx_NEWLINE_xXPatients with evidence of moderate or severe pulmonary hypertension on echocardiogramXx_NEWLINE_xXSuspected pulmonary hypertension: additional testing required, such as echocardiogramXx_NEWLINE_xXUncontrolled chronic illness such as hypertension, diabetes, or heart failureXx_NEWLINE_xXPatients who have a known cardiac shunt or pulmonary hypertensionXx_NEWLINE_xXPatients with known pulmonary hypertensionXx_NEWLINE_xXSevere pulmonary hypertension or uncontrolled systemic hypertension or respiratory distress syndromeXx_NEWLINE_xXUncontrolled hypertension (>170/100 millimeter of mercury [mm Hg]) currently or within the past 7 days, orXx_NEWLINE_xXHistory or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):\r\n* History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)Xx_NEWLINE_xXrecent history of cardiovascular distress (heart attack in past year; arrhythmia; uncontrolled hypertension)Xx_NEWLINE_xXUncontrolled hypertension.Xx_NEWLINE_xXPredisposing factors to retinal vein occlusion, including uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, and coagulopathyXx_NEWLINE_xXClinically uncontrolled hypertension in the investigator's opinion (e.g., blood pressure >160/100 mmHg; note that isolated elevated readings considered to not be indicative of uncontrolled hypertension are allowed). The following within 6 months prior to Cycle 1 Day 1:Xx_NEWLINE_xXUncontrolled chronic hypertension defined as systolic > 150 or diastolic > 90 despite optimal therapyXx_NEWLINE_xX