Role of Decreased Nitric Oxide in the Tonic Elevation of Resting Sympathetic Nerve Activity in Chronic Kidney Disease Patients
The University of Texas at Arlington
Summary
Chronic kidney disease (CKD) is associated with a higher risk of cardiovascular disease and death. An overactive sympathetic nervous system in CKD patients is one of the major mechanisms increasing the cardiovascular risks in this patient population. A potential signal driving sympathetic nerve activity (SNA) involves accumulation of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA). ADMA is elevated in CKD and is a strong, independent predictor of future cardiovascular events in these patients. . The goal of this study is to determine whether overcoming the accumulation of endogenous ADMA with acute L-arginine infusion reduces SNA in CKD patients.
Description
The central hypothesis is that accumulation of ADMA constitutes a major mechanism for the sympathetic overactivity and hypertension in patients with CKD. In this study, the investigators will determine if restoration of NO production with the infusion of L-arginine reduces SNA and blood pressure. On the experimental day, CKD patients will arrive at the laboratory fasted with no morning meds, will refrain from caffeine for 12 hours, and alcohol and physical activity for 24 hours. The collaborating physician Dr. Ashfaq Siddiqui will review subject medications and advise regarding any withholding…
Eligibility
- Age range
- 35–75 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * CKD patients classified as Stage 3 and 4 of National Kidney Foundation Classification with estimated glomerular filtration rate (GFR) between 15 and 59 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) formula based on serum creatinine, age, gender, and race. * Men and women 35 to 75 years of age Exclusion Criteria: * myocardial infarction * heart failure * anemia (hemoglobin \<8 g/dl) * cancer with current treatment * previous organ transplantation * immunosuppressant therapy * human immunodeficiency virus infection * pregnancy and/or lactat…
Interventions
- DrugL-Arginine
Arginine Hydrochloride 60% concentration injection 15 g in 25 mL, contains arginine hydrochloride 600 mg/mL in water for injections to 25 mL.
- OtherPlacebo
Saline
Locations (2)
- University of DelawareNewark, Delaware
- UT SouthwesternDallas, Texas