Endothelium-Dependent Vascular Relaxation in Normal Subjects and in Patients

Background. Patients with essential hypertension have a deficit in the endothelium-derived nitric oxide system that results in impaired endothelium-dependent vascular relaxation. The objective of this study was to determine whether this abnormality is caused by a deficiency of substrate for nitric oxide synthesis. Methods and Results. The vascular responses to acetylcholine (an endothelium-dependent vasodilator infused at 7.5, 15, and 30 pg/min) and sodium nitroprusside (a direct smooth muscle dilator infused at 0.8, 1.6, and 3.2 jtg/min) were studied during combined administration of dextrose 5% or L-arginine (substrate for nitric oxide synthesis infused at 40 jLmol/min) in 12 normal control subjects (seven men and five women; age, 49.3+7 years) and 14 hypertensive patients (nine men and five women; age, 48.4±7 years). In addition, the effect of Darginine (stereoisomer of arginine that is not a precursor of nitric oxide) on the vascular responses to acetylcholine was studied in eight normal control subjects and seven hypertensive patients. Drugs were infused into the brachial artery, and the response of the forearm vasculature was measured by strain gauge plethysmography. The vasodilator response to acetylcholine was significantly blunted in hypertensive patients compared with normal control subjects (maximum flow, 8.9±5 versus 15.7±6