Vascular smooth muscle contractile elements. Cellular regulation.

Stull, James T.; Gallagher, Patricia J.; Herring, B. Paul; Kamm, Kristine E.

doi:10.1161/01.hyp.17.6.723

Cited by 94 publications

(67 citation statements)

References 82 publications

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“…Under basal conditions, PN (10 -10 to 10 -6 M) reduced ring tension in this preparation. Moreover, under elevated tone conditions, PN was able to elicit concentrationdependent relaxation with or without the presence of endothelium, with no significant differences observed in the response [199]. These data were in agreement with studies in other arterial ring preparations from different animals [23,125,144], and are in agreement with the concept that the endothelium has no significant role in the modulation of PN responses [23].…”

Section: Vasorelaxant Properties Of Peroxyni-tritesupporting

confidence: 90%

“…The addition of calyculin A to the preparation abolished PN-induced relaxation. The findings with calyculin A, which can inhibit myosin-light-chain phosphatase [199], suggests that activation of myosin phosphatase is an additional mechanism by which PN can induce relaxation in this preparation. In these experiments the authors found that tetraethylammonium chloride, a nonspecific potassium channel inhibitor, significantly decreased PN-induced relaxations in a concentration-dependent manner, but that PN had no effect on rings that were precontracted by high concentrations of potassium chloride.…”

Section: Vasorelaxant Properties Of Peroxyni-tritementioning

confidence: 75%

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Potential Benefits of Peroxynitrite

Nossaman

Kadowitz²

2008

TOPHARMJ

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Peroxynitrite (PN) is generated by the reaction of nitric oxide (NO) and superoxide in one of the most rapid reactions in biology. Studies have reported that PN is a cytotoxic molecule that contributes to vascular injury in a number of disease states. However, it has become apparent that PN has beneficial effects including vasodilation, inhibition of platelet aggregation, inhibition of inflammatory cell adhesion, and protection against ischemia/reperfusion injury in the heart. It is our hypothesis that PN may serve to inactivate superoxide and prolong the actions of NO in the circulation. This manuscript reviews the beneficial effects of PN in the cardiovascular system. Keywords:Nitric oxide/*metabolism, nitric oxide synthase/metabolism/physiology, peroxynitrous acid/metabolism, reactive nitrogen species/metabolism, reactive oxygen species/metabolism, endothelium, vascular/drug effects/metabolism, muscle, smooth, vascular/drug effects/*metabolism, vasodilator agents/adverse effects, oxidative stress/*physiology, vasodilation/drug effects.

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Section: Vasorelaxant Properties Of Peroxyni-tritesupporting

confidence: 90%

Section: Vasorelaxant Properties Of Peroxyni-tritementioning

confidence: 75%

Potential Benefits of Peroxynitrite

Nossaman

Kadowitz²

2008

TOPHARMJ

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“…The nonmuscle or larger form ranges in size between 206 and 220 kDa (11)(12)(13)(14), and the smooth muscle or smaller form ranges in size between 125 and 155 kDa (15-18). Both classes of MLCKs have identical biochemical properties in vitro and exhibit overlapping tissue distribution patterns (11,19,20).Numerous studies have shown that smooth muscle MLCK 125-155 has multiple sites that can be phosphorylated by several kinases such as PKA, protein kinase C, and Ca 2ϩ /CaM-dependent kinase II in vitro at two residues, site A (Ser 992 ) and site B (Ser 1005 ), in the C-terminal region near the calmodulin binding domain (8,21,22). Phosphorylation at these sites results in desensitization of MLCK to activation by Ca 2ϩ / CaM.…”

mentioning

confidence: 99%

Myosin Phosphatase and Cofilin Mediate cAMP/cAMP-dependent Protein Kinase-induced Decline in Endothelial Cell Isometric Tension and Myosin II Regulatory Light Chain Phosphorylation

Goeckeler

Wysolmerski

2005

Journal of Biological Chemistry

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This study determined the effects of increased intracellular cAMP and cAMP-dependent protein kinase activation on endothelial cell basal and thrombin-induced isometric tension development. Elevation of cAMP and maximal cAMP-dependent protein kinase activation induced by 10 M forskolin, 40 M 3-isobutyl-1-methylxanthine caused a 50% reduction in myosin II regulatory light chain (RLC) phosphorylation and a 35% drop in isometric tension, but it did not inhibit thrombin-stimulated increases in RLC phosphorylation and isometric tension. Elevation of cAMP did not alter myosin light chain kinase catalytic activity. However, direct inhibition of myosin light chain kinase with KT5926 resulted in a 90% decrease in RLC phosphorylation and only a minimal decrease in isometric tension, but it prevented thrombin-induced increases in RLC phosphorylation and isometric tension development. We showed that elevated cAMP increases phosphorylation of RhoA 10-fold, and this is accompanied by a 60% decrease in RhoA activity and a 78% increase in RLC phosphatase activity. Evidence is presented that it is this inactivation of RhoA that regulates the decrease in isometric tension through a pathway involving cofilin. Activated cofilin correlates with increased F-actin severing activity in cell extracts from monolayers treated with forskolin/3-isobutyl-1-methylxanthine. Pretreatment of cultures with tautomycin, a protein phosphatase type 1 inhibitor, blocked the effect of cAMP on 1) the dephosphorylation of cofilin, 2) the decrease in RLC phosphorylation, and 3) the decrease in isometric tension. Together, these data provide in vivo evidence that elevated intracellular cAMP regulates endothelial cell isometric tension and RLC phosphorylation through inhibition of RhoA signaling and its downstream pathways that regulate myosin II activity and actin reorganization.Endothelial cells lining blood vessels form a continuous layer that constrains proteins and blood elements to the vascular lumen. Disruption of the continuous endothelial barrier leads to an increase in permeability and development of edema, a hallmark of acute and chronic inflammation. Chemical or inflammatory mediators activate signaling pathways that cause endothelial cells to contract forming gaps between adjacent cells leading to an increase in vascular permeability. Several laboratories studying methods to inhibit endothelial cell contraction and vascular permeability have demonstrated that elevation of intracellular cAMP augments barrier function and prevents increases in permeability to a wide range of inflammatory agonists. The primary pathway implicated in preventing increases in permeability is believed to occur through the activation of adenylate cyclase, accumulation of intracellular cAMP, and activation of PKA.2 Even though there are numerous reports (1-5) implicating cAMP/PKA in enhancing barrier function and inhibiting endothelial cell contraction, the mechanism by which cAMP/PKA protects vascular integrity is poorly understood.cAMP is a primary mediator of the biolo...

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“…Phosphorylation of the myosin regulatory light chain (MLC 20 ) by MLCK allows the actin-myosin interaction to proceed with resultant ATP hydrolysis, crossbridge formation and force generation. 12 The sensitivity of the contractile process to [Ca 2+ ] i can also be influenced by contractile agonists, probably through modulation of myosin phosphatase activity 13 or by mitogen activated kinase (MAP kinase) dependent phosphorylation of thin filament proteins caldesmon and calponin, 14 and there is evidence that AII can enhance ␣ 1 -adrenoceptor mediated contraction in rabbit aorta by activation of protein kinase C (PKC). 15,16 Surprisingly AII has also been reported to induce a reduction in response to potassium in rabbit mesenteric arteries by a mechanism dependent on a transcriptional process.…”

Section: Intracellular Ca 2+ ([Ca 2+ ] I )mentioning

confidence: 99%