Role of cyclooxygenase products in the regulation of vascular tone and in the endothelial vasodilator function of normal, hypertensive, and hypercholesterolemic humans

• Published in: The American journal of cardiology Vol. 89; no. 3; pp. 286 - 290
• Main Authors: Campia, Umberto, Choucair, Wassim K, Bryant, Melissa B, Quyyumi, Arshed A, Cardillo, Carmine, Panza, Julio A
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-02-2002; Elsevier; Elsevier Limited
• Subjects: Acetylcholine - administration & dosage; Acetylcholine - pharmacology; Arterial hypertension. Arterial hypotension; Aspirin - administration & dosage; Aspirin - pharmacology; Biological and medical sciences; Blood and lymphatic vessels; Blood Flow Velocity - drug effects; Brachial Artery - drug effects; Brachial Artery - physiology; Cardiology; Cardiology. Vascular system; Cholesterol - blood; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Clinical trials; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - pharmacology; Endothelium, Vascular - drug effects; Female; Forearm - blood supply; Heart; Humans; Hypercholesterolemia - physiopathology; Hypertension; Hypertension - etiology; Hypertension - physiopathology; Infusions, Intra-Arterial; Male; Medical sciences; Middle Aged; Nitroprusside - administration & dosage; Nitroprusside - pharmacology; Triglycerides - blood; Vasodilation - drug effects; Vasodilation - physiology; Vasodilator Agents - administration & dosage; Vasodilator Agents - pharmacology; Human; Hypertension; Prostaglandin-endoperoxide synthase; Prognosis; Enzyme; Pathogenesis; Cardiovascular disease; Metabolic diseases; Lipids; Hyperlipoproteinemia; Vasodilation; Endothelium; Hypercholesterolemia; Dysfunction; Oxidoreductases; Dyslipemia
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/S0002-9149(01)02229-9

A defective vascular activity of endothelial vasoactive substances is observed in essential hypertension and hypercholesterolemia, and is believed to participate in the vascular abnormalities characteristic of these conditions. The present study aimed to determine the role of cyclooxygenase (COX) products in the maintenance of vascular tone and in the endothelium-mediated vasodilation of healthy subjects, and to investigate their contribution to the endothelial dysfunction of essential hypertensive and hypercholesterolemic patients. The effects of intra-arterial aspirin (acetylsalicylic acid [ASA], 1, 3, and 10 mg/min) were assessed on basal forearm blood flow (strain gauge plethysmography) and on responses to acetylcholine (7.5, 15 and 30 μg/min) and sodium nitroprusside (0.8, 1.6 and 3.2 μg/min) in 24 normal, 23 hypertensive, and 24 hypercholesterolemic subjects. Basal forearm blood flow was not different among the 3 groups (p = 0.95). ASA resulted in a significant reduction of forearm blood flow from baseline in normal (p = 0.003), hypertensive (p = 0.001), and hypercholesterolemic subjects (p = 0.001), without any difference among the 3 groups (p = 0.90). ASA significantly improved the effect of acetylcholine in normal (p = 0.008), hypertensive (p = 0.008), and hypercholesterolemic subjects (p = 0.022), without significant difference among the 3 groups (p = 0.46). ASA did not significantly modify the vasodilator effect of sodium nitroprusside in any of the 3 groups. These findings suggest that in humans, vasodilator prostanoids actively contribute to the maintenance of basal vascular tone, whereas vasoconstrictor products of COX activity limit endothelium-dependent vasodilation. COX products do not appear to play a major role in the endothelial dysfunction of hypertensive or hypercholesterolemic patients.