Author + information
- Received June 17, 1993
- Revision received October 26, 1993
- Accepted November 1, 1993
- Published online March 15, 1994.
- Philip R. Casino, MD,
- Crescence M. Kilcoyne, RN,
- Arshed A. Quyyumi, MD,
- Jeffrey M. Koeg, MD and
- Julio A. Panza, MD∗
- ↵∗Address for correspondence: Dr. Julio A. Panza, National Institutes of Health, Bidding 10, Room 7B-15, Bethesda, Maryland 20892.
Objective. The purpose of this study was to determine whether the impaired endothelium-dependent vasodllation of hyperchoiesterolemic patients is due to decreased availability of l-arginine, the substrate for nitric oxide.
Background. Patients with hypercholesterolemia have impaired endothelium-dependent vasodilation that is related to a defect in the endothelium-derived nitric oxide system. However, the precise location of this abnormality has not been determined.
Methods. The study included 12 hypercholesterolemic patients (6men, 6 women; 52 ± 9 years old; serum cholesterol>240mg/dl) and 15 normal volunteers (8 men, 7 women; 50 ± 6 years old; serum cholesterol < 210 mg/dl. The forearm vascular responses to intraaterial infusion of acetylccholine, an endothelium-dependent vasodilator (7.5, 15, 30 μg/min), and sodium nitropruside, a direct smoth muscle dilator (0.8,1.6,3.2 μg/min) were studied before and during Infusion of l- or d-arginine (a stereoisomer of arginine that is not a nitric oxide precursor).
Results. The response to acetylcholine was lower in hypercholesterolemic patients than in control sutjects. However, no significant difference was observed with sodium nitroprusside infusion. l-Arginine augmented the response to acetylcholine in normal subjects (maximal blood flow increased from 14.4 ± 7 to 18.9 ± 10 ml/min per 100 ml, p < 0.002). In contrast, in the hypercholesterolemic patients, only a mild but not significant improvement in the response to acetylcholine was observed with the infusion of l-arginine (maximal blood flow increased from 6.8 ± 4 to 8.4 ±5ml/min per 100ml; p = 0.161; however, a similar mild but not significant change was also observed with l-arginine (maximal blood flow increased from 6.8± 4 to 8.3 ± 4 ml/min per 100 ml, p = 0.07). l-Arginine did not modify the response to sodium nitroprusside in either group.
Conclusions. The augmentation of endothelium-dependent vasodilation by l-arginine, the nitric oxide precursor, is defective in hypercholesterolemic patients. This supports the concept of an abnormal endothelium-derived nitric oxide system in hypercholesterolemia and indicates that decreased availability of nitric oxide substrate is not responsible for the impaired endothelial function in this condition.
- Received June 17, 1993.
- Revision received October 26, 1993.
- Accepted November 1, 1993.