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(Hypertension. 2006;48:1023.)
© 2006 American Heart Association, Inc.

Editorial Commentaries

Vasodilation by Hyperpolarization

Beyond NO

Arshed A. Quyyumi; Muhiddin Ozkor

From the Division of Cardiology, Emory University School of Medicine, Atlanta, Ga.

Correspondence to Arshed A. Quyyumi, MD, Professor of Medicine, Division of Cardiology, 1364 Clifton Rd, Ste D403C, Atlanta, GA 30322. E-mail aquyyum@emory.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Clinical assessment of human vascular endothelial function in vivo involves use of specific antagonists such as L-N^G monomethyl arginine (L-NMMA) and cyclooxygenase inhibition to establish the contribution of NO and prostaglandins, respectively, to either resting vascular tone, agonist-stimulated vasodilation, or physiological and metabolic vasodilation.^1–4 Even after complete inhibition of NO and prostaglandin (PG) synthesis, endothelium-dependent vasodilation persists, revealing the existence of a substantial NO- and PG-independent component that has been attributed to endothelium-derived hyperpolarizing factor (EDHF) release. Prime candidate EDHFs that often differ by species and circulatory beds have been extensively reviewed (Figure).^5,6

View larger version (24K):   Mechanisms of potential endothelial cell mediated relaxation/hyperpolarization. Agonist (bradykinin) or shear stress increases the activity of endothelial nNO synthase (eNOS) and cyclooxygenase (COX), providing NO and prostacyclin-mediated dilation. There are multiple potential EDHF pathways. Agonist (bradykinin) or shear stress–mediated increases in intracellular calcium activates phospholipase A2 (PLC) to produce arachadonic acid. Its metabolism by cytochrome P450 2C (CYP4502c) generates EETs that can stimulate KCa channels in endothelial and smooth muscle cells. EETs may also directly activate gap junctions(Gap). The increase in K+ in the interstitium may activate KCa,channels, KIR, or the Na+-K+ pump on smooth muscle cells and cause hyperpolarization. The action of eNOS (with cofactor tetrahydrobiopterin [BH4]) and oxidases on oxygen (O2) produces the reactive oxygen species superoxide (O2·–). Hydrogen peroxide (H2O2) generated by dismutation of superoxide anions (O2·–) by superoxide dismutase (SOD) can also cause hyperpolarization by activating endothelial and smooth . . . [Full Text of this Article]

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