FK506 (Tacrolimus) in Pulmonary Arterial Hypertension

Inclusion Criteria: 1. Age ≥ 18 and \< 70 years 2. Diagnosis of WHO Group I Pulmonary Arterial Hypertension (PAH) (Idiopathic (I)PAH, Heritable PAH (including Hereditary Hemorrhagic Telangiectasia), Associated (A)PAH (including collagen vascular disorders, drugs+toxins exposure, congenital heart disease, and portopulmonary disease). 3. Stable on active PAH treatment including any prostacycline or phosphodiesterase inhibitors and the endothelin antagonist Ambrisentan alone or in combination (stability defined as: \<10% change in 6MWD, no change in NYHA class, no hospitalization or addition of PAH therapy for at least 3 months). 4. Previous Right Heart Catheterization that documented: 1. Mean PAP ≥ 25 mmHg. 2. Pulmonary capillary wedge pressure \< 15 mmHg. 3. Pulmonary Vascular Resistance ≥ 3.0 Wood units or 240 dynes/sec/cm5 5. WHO functional class I to IV as judged by the investigator. Exclusion Criteria: 1. WHO Group II - V Pulmonary Hypertension. 2. Current or prior experimental PAH treatments within the last 6 months (including but not limited to tyrosine kinase inhibitors, rho-kinase inhibitors, or cGMP modulators). 3. Current active treatment with the dual endothelin receptor antagonist bosentan. 4. TLC \< 60% predicted; if TLC b/w 60 and 70% predicted, high resolution computed tomography must be available to exclude significant interstitial lung disease. 5. FEV1 / FVC \< 70% predicted and FEV1 \< 60% predicted 6. Significant left-sided heart disease (based on screening Echocardiogram): 1. Significant aortic or mitral valve disease 2. Diastolic dysfunction ≥ Grade II 3. LV systolic function \< 45% 4. Pericardial constriction 5. Restrictive cardiomyopathy 6. Significant coronary disease with demonstrable ischemia. 7. Chronic renal insufficiency defined as an estimated creatinine clearance \< 30 ml/min (by MDRD equation). 8. Current atrial arrhythmias not under optimal control. 9. Uncontrolled systemic hypertension: SBP \> 160 mm or DBP \> 100mm 10. Severe hypotension: SBP \< 80 mmHg. 11. Pregnant or breast-feeding. 12. Psychiatric, addictive, or other disorder that compromises patient's ability to provide informed consent, follow study protocol, and adhere to treatment instructions. 13. Active cyclosporine use. 14. Known allergy or hypersensitivity to FK-506. 15. Planned initiation of cardiac or pulmonary rehabilitation during period of study. 16. Human Immunodeficiency Virus infection. 17. Moderate to severe hepatic dysfunction with a Pugh score \>10. 18. Hyperkalemia defined as Potassium \> 5.1 mEq/L at screening . 19. Known active infection requiring antibiotic, antifungal, or antiviral therapies. 20. Co-morbid conditions that would impair a patient's exercise performance and ability to assess WHO functional class, including but not limited to chronic low-back pain or peripheral musculoskeletal problems.