Regulation of vascular tone by nitric oxide (NO) derived from endothelium and nerve : Physiol1ogical and pathophysiological roles of vascular endothelium-derived vasoactive substance

The endothelium is an organ with a key role in the maintenance of cardiovascular health through the regulation of vascular tone, vascular resistance, blood flow, and arterial pressure. These functions are related with the synthesis and release of vasoactive molecules, mainly vasodilators like nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Both factors are released and diffused from endothelial cells to the smooth muscle cells, where there is a subsequent activation of signaling pathways that finally decrease the intracellular calcium to induce the vascular relaxation. The study of the molecular mechanisms that underlie the endothelial function still is in development, but from the evidence obtained from the endothelial cells in vitro studies are possible to partially describe the pathways to regulate the physiological endothelial function and the disturbances in pathological conditions. In this mini-review, we describe the main mechanisms for NO synthesis and the role of potassium channels related with EDHF. We include schemes and graphical summaries for better understanding of the molecular regulation of vascular tone in the human cardiovascular system.

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Interactions Between Nitric Oxide and Endothelin in the Regulation of Vascular Tone of Human Resistance Vessels In Vivo

Hypertension ◽

10.1161/01.hyp.35.6.1237 ◽

2000 ◽

Vol 35 (6) ◽

pp. 1237-1241 ◽

Cited By ~ 90

Author(s):

Carmine Cardillo ◽

Crescence M. Kilcoyne ◽

Richard O. Cannon ◽

Julio A. Panza

Keyword(s):

Nitric Oxide ◽

Vascular Tone ◽

Resistance Vessels ◽

Regulation Of Vascular Tone

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Role of arachidonic acid lipoxygenase metabolites in the regulation of vascular tone

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00349.2009 ◽

2009 ◽

Vol 297 (2) ◽

pp. H495-H507 ◽

Cited By ~ 58

Author(s):

Yuttana Chawengsub ◽

Kathryn M. Gauthier ◽

William B. Campbell

Keyword(s):

Arachidonic Acid ◽

Smooth Muscle ◽

Vascular Endothelium ◽

Vascular Tone ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Epoxyeicosatrienoic Acid ◽

Regulation Of Vascular Tone ◽

Small Conductance

Stimulation of vascular endothelial cells with agonists such as acetylcholine (ACh) or bradykinin or with shear stress activates phospholipases and releases arachidonic acid (AA). AA is metabolized by cyclooxygenases, cytochrome P-450s, and lipoxygenases (LOs) to vasoactive products. In some arteries, a substantial component of the vasodilator response is dependent on LO metabolites of AA. Nitric oxide (NO)- and prostaglandin (PG)-independent vasodilatory responses to ACh and AA are reduced by inhibitors of LO and by antisense oligonucleotides specifically against 15-LO-1. Vasoactive 15-LO metabolites derived from the vascular endothelium include 15-hydroxy-11,12-epoxyeicosatrienoic acid (15-H-11,12-HEETA) that is hydrolyzed by soluble epoxide hydrolase to 11,12,15-trihydroxyeicosatrienoic acid (11,12,15-THETA). HEETA and THETA are endothelium-derived hyperpolarizing factors that induce vascular relaxations by activation of smooth muscle apamin-sensitive, calcium-activated, small-conductance K+ channels causing hyperpolarization. In other arteries, the 12-LO metabolite 12-hydroxyeicosatetraenoic acid is synthesized by the vascular endothelium and relaxes smooth muscle by large-conductance, calcium-activated K+ channel activation. Thus formation of vasodilator eicosanoids derived from LO pathways contributes to the regulation of vascular tone, local blood flow, and blood pressure.

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