The role of nitric oxide in endothelium-dependent vasodilation of hypercholesterolemic patients.

Abstract

BACKGROUND:

Patients with hypercholesterolemia have a reduced response to endothelium-dependent vasodilators. However, the regulatory function of the endothelium on vascular tone is mediated through the release of several vasoactive substances; therefore, a reduced response to endothelium-dependent agents does not identify which of the factors released by the endothelium is involved in this abnormality.

METHODS AND RESULTS:

To investigate the role of nitric oxide in the endothelium-dependent vasodilation in hypercholesterolemia, we studied the effect of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of endothelial nitric oxide synthesis, on basal vascular tone and on the responses to acetylcholine, an endothelium-dependent vasodilator, and to sodium nitroprusside, a direct smooth muscle dilator. The study included 33 hypercholesterolemic patients (17 men; 51 +/- 8 years; plasma cholesterol, > or = 240 mg/dL) and 23 normal controls (12 men; 48 +/- 7 years; plasma cholesterol, < 210 mg/dL). Drugs were infused into the brachial artery, and the response of the forearm vasculature was measured by strain-gauge plethysmography. Basal blood flow and vascular resistance 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-NMMA were not significantly different between the two groups. L-NMMA markedly blunted the response to acetylcholine in normals (maximum flow decreased from 16.4 +/- 8 to 7.0 +/- 3; P < .005); however, the arginine analogue did not significantly modify the response to acetylcholine in the hypercholesterolemic patients (maximum flow, 11.1 +/- 8 versus 10.0 +/- 8). L-NMMA did not modify the vasodilator response to sodium nitroprusside in either controls or patients.

CONCLUSIONS:

These findings indicate that hypercholesterolemic patients have a defect in the bioactivity of nitric oxide that may explain their impaired endothelium-dependent vascular relaxation.

• Authors: P R Casino, C M Kilcoyne, A A Quyyumi, J M Hoeg, J A Panza
• Journal: Circulation (Circulation) Vol. 88 Issue 6 Pg. 2541-7 (Dec 1993) ISSN: 0009-7322 [Print] United States
• PMID: 8252665 (Publication Type: Journal Article)

Chemical References

• Nitroprusside
• omega-N-Methylarginine
• Nitric Oxide
• Arginine
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Adult
• Aged
• Arginine (analogs & derivatives, pharmacology)
• Blood Flow Velocity (drug effects)
• Endothelium, Vascular (drug effects, physiopathology)
• Female
• Forearm (blood supply)
• Humans
• Hypercholesterolemia (physiopathology)
• Male
• Middle Aged
• Nitric Oxide (antagonists & inhibitors, physiology)
• Nitroprusside (pharmacology)
• Vascular Resistance (drug effects)
• Vasodilation (drug effects, physiology)
• omega-N-Methylarginine