scholarly journals Calcium-Activated Potassium Channels and the Regulation of Vascular Tone

Physiology ◽  
2006 ◽  
Vol 21 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Jonathan Ledoux ◽  
Matthias E. Werner ◽  
Joseph E. Brayden ◽  
Mark T. Nelson
Keyword(s):  
Smooth Muscle ◽  
Potassium Channels ◽  
Vascular Function ◽  
Vascular Tone ◽  
Calcium Signals ◽  
Different Types ◽  
Calcium Activated Potassium Channels ◽  
Regulation Of Vascular Tone

Different calcium signals in the endothelium and smooth muscle target different types of Ca2+-sensitive K+ channels to modulate vascular function. These differential calcium signals and targets represent multilayered opportunities for prevention and/or treatment of vascular dysfunctions.

Intracellular mechanisms involved in the regulation of vascular smooth muscle tone

1995 ◽  
Vol 73 (5) ◽  
pp. 565-573 ◽  
Author(s):  
Michael P. Walsh ◽  
Gary J. Kargacin ◽  
John Kendrick-Jones ◽  
Thomas M. Lincoln
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Cyclic Gmp ◽  
Vascular Tone ◽  
Light Chains ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Regulation Of Vascular Tone

Vascular smooth muscle contraction is thought to occur by a mechanism similar to that described for striated muscles, i.e., via a cross-bridge cycling – sliding filament mechanism. This symposium focused on Ca2+ signalling and the role of intracellular free Ca2+ concentration, [Ca2+]i, in regulating vascular tone: how contractile stimuli leading to an increase in [Ca2+]i trigger vasoconstriction and how relaxant signals reduce [Ca2+]i causing vasodilation. M.P. Walsh opened the symposium with an overview emphasizing the central role of myosin phosphorylation–dephosphorylation in the regulation of vascular tone and identifying recent developments concerning regulation of [Ca2+]i, Ca2+ sensitization and desensitization of the contractile response, Ca2+-independent protein kinase C induced contraction, and direct regulation of cross-bridge cycling by the thin filament associated proteins caldesmon and calponin. The remainder of the symposium focused on three specific areas related to the regulation of vascular tone: Ca2+ signalling in relation to smooth muscle structure, structure–function relations of myosin, and the role of cyclic GMP (cGMP) dependent protein kinase. G.J. Kargacin described how smooth muscle cells are structured and how second messenger signals such as Ca2+ might be modified or influenced by this structure. J. Kendrick-Jones then discussed the results of mutagenesis studies aimed at understanding how the myosin light chains, particularly the phosphorylatable (Ca2+–calmodulin dependent) regulatory light chains, control myosin. The vasorelaxant effects of signalling molecules such as β-adrenergic agents and nitrovasodilators are mediated by cyclic nucleotide dependent protein kinases, leading principally to a reduction in [Ca2+]i. T.M. Lincoln described the roles of cyclic nucleotide dependent protein kinases, in particular cyclic GMP dependent protein kinase, in vasodilation.Key words: vascular smooth muscle, regulation of contraction, smooth muscle structure, calcium, cyclic GMP, myosin.

scholarly journals Transglutaminase 2 Inhibitor LDN 27219 Age-Dependently Lowers Blood Pressure and Improves Endothelium-Dependent Vasodilation in Resistance Arteries

Hypertension ◽  
2021 ◽  
Vol 77 (1) ◽  
pp. 216-227 ◽  
Author(s):  
Estéfano Pinilla ◽  
Simon Comerma-Steffensen ◽  
Judit Prat-Duran ◽  
Luis Rivera ◽  
Vladimir V. Matchkov ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Potassium Channels ◽  
Vascular Function ◽  
Transglutaminase 2 ◽  
Mesenteric Arteries ◽  
Resistance Arteries ◽  
Closed Conformation ◽  
Open Conformation ◽  
Age Related

Transglutaminase 2 (TG2) is an enzyme which in the open conformation exerts transamidase activity, leading to protein cross-linking and fibrosis. In the closed conformation, TG2 participates in transmembrane signaling as a G protein. The unspecific transglutaminase inhibitor cystamine causes vasorelaxation in rat resistance arteries. However, the role of TG2 conformation in vascular function is unknown. We investigated the vascular effects of selective TG2 inhibitors by myography in isolated rat mesenteric and human subcutaneous resistance arteries, patch-clamp studies on vascular smooth muscle cells, and blood pressure measurements in rats and mice. LDN 27219 promoted the closed TG2 conformation and inhibited transamidase activity in mesenteric arteries. In contrast to TG2 inhibitors promoting the open conformation (Z-DON, VA5), LDN 27219 concentration-dependently relaxed rat and resistance human arteries by a mechanism dependent on nitric oxide, large-conductance calcium-activated and voltage-gated potassium channels 7, lowering blood pressure. LDN 27219 also potentiated acetylcholine-induced relaxation by opening potassium channels in the smooth muscle; these effects were abolished by membrane-permeable TG2 inhibitors promoting the open conformation. In isolated arteries from 35- to 40-week-old rats, transamidase activity was increased, and LDN 27219 improved acetylcholine-induced relaxation more than in younger rats. Infusion of LDN 27219 decreased blood pressure more effectively in 35- to 40-week than 12- to 14-week-old anesthetized rats. In summary, pharmacological modulation of TG2 to the closed conformation age-dependently lowers blood pressure and, by opening potassium channels, potentiates endothelium-dependent vasorelaxation. Our findings suggest that promoting the closed conformation of TG2 is a potential strategy to treat age-related vascular dysfunction and lowers blood pressure.

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

2009 ◽  
Vol 297 (2) ◽  
pp. H495-H507 ◽  
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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