Neurovascular Regulation During Exercise in Humans With Chronic Kidney Disease: Sympatholysis in CKD

Inclusion Criteria:

* patients with CKD (Stages III and IV), kidney transplant recipients with varying degrees of kidney function, or persons without kidney disease as matched study controls
* sedentary and do not regularly exercise (defined as exercising \< 20 minutes twice per week)
* CKD patients must have stable renal function (no greater than a decline of estimated glomerular filtration (eGFR) of 1 cc/min/1.73 m2 per month over the prior 6 months) and baseline serum bicarbonate 22-24 mmol/L
* comorbid hypertension

Exclusion Criteria:

* severe CKD (eGFR\<15 cc/min)
* metabolic alkalosis
* current treatment with bicarbonate
* ongoing drug or alcohol abuse
* diabetic neuropathy, autonomic dysfunction
* any serious disease that might influence survival
* anemia with hemoglobin \<10 g/dL
* clinical evidence of heart failure
* volume overload or ejection fraction below 45%
* symptomatic heart disease by EKG, stress test, and/or history
* treatment with central α-agonists (clonidine)
* myocardial infarction or cerebrovascular accident within the past six months
* uncontrolled hypertension (BP\>170/100 mm Hg)
* low BP\<100/50 mm Hg
* surgery within the past 3 months
* pregnancy or plans to become pregnant
* inability to exercise on a stationary bicycle
* contraindication to temporary withdrawal of α- and β-blockers
* peripheral arterial disease
* class 3 obesity (BMI\>40)
* hypo- or hyperkalemia (K\<3.5meq/L, K\>5.0 meq/L)
* current use of immunosuppressive medications (including but not limited to steroids, cyclophosphamide, calcineurin inhibitors, mycophenolate, biologics, methotrexate, etc)
* arteriovenous (AV) fistula/graft
* any contraindication to MR scanning including cardiac pacemaker, cochlear implants, neurostimulators, implanted devices with metal, any metal in the body that could pose a hazard during scanning, history of claustrophobia