EFFECT OF INCREASED AVAILABILITY OF ENDOTHELIUM-DERIVED NITRIC-OXIDE PRECURSOR ON ENDOTHELIUM-DEPENDENT VASCULAR RELAXATION IN NORMAL SUBJECTS AND IN PATIENTS WITH ESSENTIAL-HYPERTENSION

Background. Patients with essential hypertension have a deficit in the endothelium-derived nitric oxide system that results in impaired endo thelium-dependent vascular relaxation. The objective of this study was to determine whether this abnormality is caused by a deficiency of su bstrate for nitric oxide synthesis. Methods and Results. The vascular responses to acetylcholine (an endothelium-dependent vasodilator infus ed at 7.5, 15, and 30 mug/min) and sodium nitroprusside (a direct smoo th muscle dilator infused at 0.8, 1.6, and 3.2 mug/min) were studied d uring combined administration of dextrose 5% or L-arginine (substrate for nitric oxide synthesis infused at 40 mumol/min) in 12 normal contr ol subjects (seven men and five women; age, 49.3+/-7 years) and 14 hyp ertensive patients (nine men and five women; age, 48.4+/-7 years). In addition, the effect Of D-arginine (stereoisomer of arginine that is n ot a precursor of nitric oxide) on the vascular responses to acetylcho line was studied in eight normal control subjects and seven hypertensi ve patients. Drugs were infused into the brachial artery, and the resp onse of the forearm vasculature was measured by strain gauge plethysmo graphy. The vasodilator response to acetylcholine was significantly bl unted in hypertensive patients compared with normal control subjects ( maximum flow, 8.9+/-5 versus 15.7+/-6 mL . min-1 . 100 mL-1, respectiv ely; p < 0.007); however, no difference was observed in the response t o sodium nitroprusside (11.4+/-6 and 11.7+/-mL . min-1 . 100 mL-1, res pectively). L-Arginine did not significantly change basal blood flow o r vascular resistance in either group. In normal control subjects, the infusion Of L-arginine significantly augmented the vasodilator respon se to acetylcholine (maximum How, 15.7+/-6 versus 21.4+/-8 mL . min-1 . 100 ml-1 before and after L-arginine, respectively p < 0.001). In co ntrast, in hypertensive patients, the infusion of L-arginine did not a lter the response to acetylcholine (maximum flow, 8.9+/-5 and 8.4+/-4 mL . min-1 . 100 mL-1 before and after L-arginine, respectively). The administration of L-arginine did not modify the response to sodium nit roprusside in either group. Similarly, the infusion of D-arginine did not alter the response to acetylcholine in either group. Conclusions. In normal humans, availability of substrate for production of nitric o xide is a rate-limiting step for endothelium-dependent vascular relaxa tion. In contrast, increased availability of nitric oxide precursor do es not modify endothelium-mediated vasodilation in hypertensive patien ts. These findings provide further evidence of a defect in the endothe lium-derived nitric oxide system in hypertension and indicate that thi s abnormality is not related to decreased availability of substrate fo r nitric oxide production.