THE ROLE OF NITRIC-OXIDE IN ENDOTHELIUM-DEPENDENT VASODILATION OF HYPERCHOLESTEROLEMIC PATIENTS

Citation
Pr. Casino et al., THE ROLE OF NITRIC-OXIDE IN ENDOTHELIUM-DEPENDENT VASODILATION OF HYPERCHOLESTEROLEMIC PATIENTS, Circulation, 88(6), 1993, pp. 2541-2547
Citations number
43
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiac & Cardiovascular System",Hematology
Journal title
ISSN journal
0009-7322
Volume
88
Issue
6
Year of publication
1993
Pages
2541 - 2547
Database
ISI
SICI code
0009-7322(1993)88:6<2541:TRONIE>2.0.ZU;2-L
Abstract
Background. Patients with hypercholesterolemia have a reduced response to endothelium-dependent vasodilators. However, the regulatory functi on of the endothelium on vascular tone is mediated through the release of several vasoactive substances; therefore, a reduced response to en dothelium-dependent agents does not identify which of the factors rele ased by the endothelium is involved in this abnormality. Methods and R esults. To investigate the role of nitric oxide in the endothelium-dep endent vasodilation in hypercholesterolemia, we studied the effect of N-G-monomethyl-L-arginine (L-NMMA), an inhibitor of endothelial nitric oxide synthesis, on basal vascular tone and on the responses to acety lcholine, an endothelium-dependent vasodilator, and to sodium nitropru sside, a direct smooth muscle dilator. The study included 33 hyperchol esterolemic patients (17 men; 51+/8 years; plasma cholesterol, greater than or equal to 240 mg/dL) and 23 normal controls (12 men; 48+/-7 ye ars; plasma cholesterol, <210 mg/dL). Drugs were infused into the brac hial artery, and the response of the forearm vasculature was measured by strain-gauge plethysmography. Basal blood flow and vascular resista nce were similar in hypercholesterolemic patients and normal controls (3.1+/-1 versus 2.6+/-0.8 mL/min per 100 mL and 32.1+/-13 versus 36.1/-12 mm Hg/mL(-1).min(-1) 100 mL(-1), respectively). The reduction in basal blood flow and increase in vascular resistance produced by L-NMM A were not significantly different between the two groups. L-NMMA mark edly blunted the response to acetylcholine in normals (maximum flow de creased from 16.4+/-8 to 7.0+/-3; P<.005); however, the arginine analo gue did not significantly modify the response to acetylcholine in the hypercholesterolemic patients (maximum how, 11.1+/-8 versus 10.0+/-8). L-NMMA did not modify the vasodilator response to sodium nitroprussid e in either controls or patients. Conclusions. These findings indicate that hypercholesterolemic patients have a defect in the bioactivity o f nitric oxide that may explain their impaired endothelium-dependent v ascular relaxation.