Safety and Cardiovascular Efficacy of Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD

Inclusion Criteria 1. Maintenance hemodialysis therapy for end-stage renal disease 2. Age 18-85 years 3. ≥ 90 days since dialysis initiation 4. Ability to provide informed consent 5. Pre-dialysis seated systolic blood pressure measurements must be ≥ 120 mm Hg in the 2 weeks before enrollment and on the day of randomization. Exclusion Criteria 1. Serum potassium ≥6.5 mEq/L within 2 months prior to screening 2. Unscheduled dialysis for hyperkalemia within the 3 months prior to screening 3. Hypotension defined as pre-dialysis SBP \<100 mm Hg (seated measurement) within 4 weeks prior to enrollment 4. Recurrent intra-dialytic hypotension, defined as systolic blood pressure \<80 mm Hg during ≥3 dialysis sessions per 30-day rolling period or treatment for either hypotension or symptoms of hypotension if systolic blood pressure is \< 100 mm Hg during ≥3 dialysis sessions per 30-day rolling period. 5. Mitral valve repair or replacement 6. Severe mitral valve disease by echocardiography, coronary angiography or cardiac magnetic resonance imaging 7. Prior coronary artery bypass graft 8. Anticipated kidney transplant, change to peritoneal dialysis, or transfer to another dialysis unit within 6 months 9. Expected survival \< 6 months 10. Allergy to study medications (ISD, HY, adenosine/diprimidole) 11. Active use of sildenafil, vardenafil or tadalafil 12. History of severe aortic stenosis or other cause of LV outflow obstruction 13. Pregnancy, anticipated pregnancy, or breastfeeding, confirmed by serum pregnancy test on the day of PET scan 14. Incarceration 15. Participation in another intervention study 16. Use of monoamine oxidase inhibitors 17. Contraindication to adenosine including * 2nd or 3rd degree heart block, sick sinus syndrome or symptomatic bradycardia (without a functioning pacemaker) * moderate or severe asthma * chronic obstructive pulmonary disease 18. Active use of any of the study medications unless participant and physician willing to discontinue prior to enrollment.