Endothelium-Derived Hyperpolarizing Factor Determines Resting and Stimulated Forearm Vasodilator Tone in Health and in Disease

• Published in: Circulation (New York, N.Y.) N.Y.), 2011-05, Vol.123 (20), p.2244-2253
• Main Authors: OZKOR, Muhiddin A, MURROW, Jonathan R, RAHMAN, Ayaz M, KAVTARADZE, Nino, JI LIN, MANATUNGA, Amita, QUYYUMI, Arshed A
• Format: Article
• Language: English
• Subjects: Acetylcholine - administration & dosage; Adult; Biological and medical sciences; Biological Factors - physiology; Blood and lymphatic vessels; Bradykinin - administration & dosage; Cardiology. Vascular system; Cytochrome P-450 Enzyme System - physiology; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Enzyme Inhibitors - administration & dosage; Female; Forearm - blood supply; Humans; Hypercholesterolemia - epidemiology; Hypercholesterolemia - physiopathology; Male; Medical sciences; Middle Aged; Nitric Oxide - physiology; omega-N-Methylarginine - administration & dosage; Plethysmography; Potassium Channel Blockers - administration & dosage; Potassium Channels - physiology; Regional Blood Flow - drug effects; Regional Blood Flow - physiology; Risk Factors; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Tetraethylammonium - administration & dosage; Vasodilation - drug effects; Vasodilation - physiology; Young Adult
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circulationaha.110.990317

We assessed the contribution of endothelium-derived hyperpolarizing factors to resting and agonist-stimulated vasodilator tone in health and disease. Tetraethylammonium chloride (TEA) was used to inhibit K(+)(Ca) channel activation and fluconazole was used to inhibit cytochrome P450 2C9-mediated epoxyeicosatrienoic acid synthesis. We hypothesized that endothelium-derived hyperpolarizing factors contribute to resting vascular tone by K(+)(Ca) channel activation and epoxyeicosatrienoic acid release and that endothelium-derived hyperpolarizing factors compensate for reduced nitric oxide bioavailability at rest and with endothelium-dependent vasodilators. In 103 healthy subjects and 71 nonhypertensive subjects with multiple risk factors, we measured resting forearm blood flow (FBF) using venous occlusion plethysmography before and after intra-arterial infusions of N(G)-monomethyl-l-arginine (L-NMMA), TEA, fluconazole, and their combination. The effects of these antagonists on resting FBF and on bradykinin- and acetylcholine-mediated vasodilation were studied. Resting FBF decreased with TEA and L-NMMA in all subjects (P