This proposal will test the hypothesis that chronic treatment with sildenafil with and without the use of nitric oxide substrate, L-arginine, protects against fatty acid induced impairment of endothelial function, improves insulin-stimulated microvascular recruitment, insulin sensitivity and glucose uptake in CD36 rs3211938 G-allele carriers.
Name: Sildenafil Citrate
Description: The primary endpoint is the change in microvascular blood volume (ΔMBV) during insulin infusion from baseline, an index of insulin-stimulated microvascular recruitment.Measure: insulin-stimulated microvascular recruitment. Time: 4 weeks
Description: Glucose infusion rate during hyperinsulinemic euglycemic clampMeasure: Insulin sensitivity Time: 4 weeks
Single Group Assignment
There is one SNP
CD36 in Nutrient Delivery and Its Dysfunction This proposal will test the hypothesis that chronic treatment with sildenafil with and without the use of nitric oxide substrate, L-arginine, protects against fatty acid induced impairment of endothelial function, improves insulin-stimulated microvascular recruitment, insulin sensitivity and glucose uptake in CD36 rs3211938 G-allele carriers.
- Cardiovascular disease such as myocardial infarction, presence of angina pectoris, significant arrhythmia, congestive heart failure (left ventricular hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy - History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack - History or presence of immunological or hematological disorders - Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult - Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month) - History of alcohol or drug abuse - Mental conditions rendering a subject unable to understand the nature, scope and possible consequences of the study - Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, unlikelihood of completing the study, and investigator discretion Insulin Resistance Endothelial Dysfunction Insulin Resistance Subjects carrying the G-allele of CD36 coding SNP rs3211938 that results in 50% reduction of CD36 levels in ~25% of African Americans have endothelial dysfunction.