Protein kinase C potentiates stretch-induced cerebral artery tone by increasing intracellular sensitivity to Ca2+

Laher, Ismail; Vorkapic, Peter; Dowd, A.; Bevan, John A.

doi:10.1016/0006-291x(89)91071-1

Cited by 30 publications

(24 citation statements)

References 12 publications

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“…Even though we do not know the precise mechanism through which pressure induces the production of 20-HETE to initiate the myogenic response, we do know that PKC and perhaps inositol 1,4,5-trisphosphate are involved (11,25,29,30,39). The vasoconstriction action of pressure can be linked to depolarization (19,22) subsequent to the release of 20-HETE and the activation and translocation of PKC (15,21,26,31,34).…”

Section: Role Of Pkc and The Mechanism Of Action Of 20-hete In Cerebrmentioning

confidence: 99%

“…The other gene of interest is the ADD-3 gene, which similar to the DUSP-5, is also expressed in brain tissue and cerebral vessels (unpublished findings), functions to promote the spectrin-actin binding, and controls the rate of actin polymerization by capping actin filaments at the plasma membrane (35,36), thereby in a position to initiate myogenic response. Adducin function is Ca 2ϩ and calmodulin dependent and contains the MARCKS domain (35,36), which is a target for phosphorylation by a family of kinases including PKC, tyrosine kinase, and [Rho]-kinase, or similar molecules that are important in signaling pressure-or stretch-induced myogenic responses (13, 25,29,30,38,55). Despite the fact that very little is known about the functional roles of DUSP-5 and ADD-3 genes in vasoregulation, it is important that we study and unravel the potential roles of the ADD-3 and DUSP-5 genes in the development and maintenance of pressure-induced myogenic autoregulation in the cerebral circulation.…”

Section: The Entire Myogenic Cascade In Cerebral Arteriolesmentioning

confidence: 99%

“…20-hydroxyeicosatetraenoic acid; cytochrome P-450 4A; ion channels; membrane potential STEPWISE INCREASE OF transmural pressure in isolated and cannulated cerebral arteries gives rise to a series of signaling events that culminate in stepwise constriction of the arterial segments. These arterial muscle signaling events include membrane depolarization, reduction in outward K ϩ current, increase in inward Ca 2ϩ current (via L-type Ca 2ϩ channels), translocation of PKC and phosphorylation, and elevation of inositol 1,4,5-trisphosphate and diacylglycerol, all of which are related to the activation of arterial muscle and allow arterial diameter to track changes in blood pressure, thereby maintaining blood flow relatively constant (3, 5,19,25,(27)(28)(29)(30)(31)44). The signaling pathway mediating these events involves the production of the potent vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) (15,21,23,26,34).…”

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confidence: 99%

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Pressure-induced myogenic tone and role of 20-HETE in mediating autoregulation of cerebral blood flow

Harder

Narayanan

Gebremedhin

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Harder DR, Narayanan J, Gebremedhin D. Pressure-induced myogenic tone and role of 20-HETE in mediating autoregulation of cerebral blood flow. Am J Physiol Heart Circ Physiol 300: H1557-H1565, 2011. First published January 21, 2011; doi:10.1152/ajpheart.01097.2010.-While myogenic force in response to a changing arterial pressure has been described early in the 20th century, it was not until 1984 that the effect of a sequential increase in intraluminal pressure on cannulated cerebral arterial preparations was found to result in pressure-dependent membrane depolarization associated with spike generation and reduction in lumen diameter. Despite a great deal of effort by different laboratories and investigators, the identification of the existence of a mediator of the pressure-induced myogenic constriction in arterial muscle remained a challenge. It was the original finding by our laboratory that demonstrated the capacity of cerebral arterial muscle cells to express the cytochrome P-450 4A enzyme that catalyzes the formation of the potent vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid, the production of which in cerebral arterial muscle cells increases with the elevation in intravascular pressure. 20-HETE activates protein kinase C and causes the inhibition of Ca 2ϩ -activated K ϩ channels, depolarizes arterial muscle cell membrane, and activates L-type Ca 2ϩ channel to increase intracellular Ca 2ϩ levels and evoke vasoconstriction. The inhibition of 20-HETE formation attenuates pressureinduced arterial myogenic constriction in vitro and blunts the autoregulation of cerebral blood flow in vivo. We suggest that the formation and action of cytochrome P-450-derived 20-HETE in cerebral arterial muscle could play a critically important role in the control of cerebral arterial tone and the autoregulation of cerebral blood flow under physiological conditions. 20-hydroxyeicosatetraenoic acid; cytochrome P-450 4A; ion channels; membrane potential STEPWISE INCREASE OF transmural pressure in isolated and cannulated cerebral arteries gives rise to a series of signaling events that culminate in stepwise constriction of the arterial segments. These arterial muscle signaling events include membrane depolarization, reduction in outward K ϩ current, increase in inward Ca 2ϩ current (via L-type Ca 2ϩ channels), translocation of PKC and phosphorylation, and elevation of inositol 1,4,5-trisphosphate and diacylglycerol, all of which are related to the activation of arterial muscle and allow arterial diameter to track changes in blood pressure, thereby maintaining blood flow relatively constant (3, 5,19,25,(27)(28)(29)(30)(31)44). The signaling pathway mediating these events involves the production of the potent vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) (15,21,23,26,34). These series of signaling reactions maintain blood flow constant despite wide fluctuations in arterial pressure. The reasons for such maintenance of blood flow can be explained both physiologically as well as teleologically...

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Section: Role Of Pkc and The Mechanism Of Action Of 20-hete In Cerebrmentioning

confidence: 99%

Section: The Entire Myogenic Cascade In Cerebral Arteriolesmentioning

confidence: 99%

mentioning

confidence: 99%

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Pressure-induced myogenic tone and role of 20-HETE in mediating autoregulation of cerebral blood flow

Harder

Narayanan

Gebremedhin

2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…3 A rise in MT has been associated with diseases, such as hypertension 4 and diabetes mellitus. 5 Signaling mechanisms contributing to MT require opening of mechanosensitive channels, 6,7 membrane depolarization, activation of voltage-operated calcium channels, 8,9 calcium entry, 10 protein kinase C, 11 and phospholipase C activation, 12 as well as calcium-sensitization of the contractile apparatus. 3 The cytoskeleton plays an important role in MT.…”

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confidence: 99%

Selective Involvement of Serum Response Factor in Pressure-Induced Myogenic Tone in Resistance Arteries

Retailleau

Toutain

Galmiche

et al. 2013

ATVB

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Objective-In resistance arteries, diameter adjustment in response to pressure changes depends on the vascular cytoskeleton integrity. Serum response factor (SRF) is a dispensable transcription factor for cellular growth, but its role remains unknown in resistance arteries. We hypothesized that SRF is required for appropriate microvascular contraction. Methods and Results-We used mice in which SRF was specifically deleted in smooth muscle or endothelial cells, and their control. Myogenic tone and pharmacological contraction was determined in resistance arteries. mRNA and protein expression were assessed by quantitative real-time PCR (qRT-PCR) and Western blot. Actin polymerization was determined by confocal microscopy. Stress-activated channel activity was measured by patch clamp. Myogenic tone developing in response to pressure was dramatically decreased by SRF deletion (5.9±2.3%) compared with control (16.3±3.2%). This defect was accompanied by decreases in actin polymerization, filamin A, myosin light chain kinase and myosin light chain expression level, and stress-activated channel activity and sensitivity in response to pressure. Contractions induced by phenylephrine or U46619 were not modified, despite a higher sensitivity to p38 blockade; this highlights a compensatory pathway, allowing normal receptor-dependent contraction. Conclusion-This

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“…Previous studies (17,29,37) indicated that myogenic tone was highly dependent on an elevation of intracellular free Ca 2ϩ concentration ([Ca 2ϩ ] i ). However, it has also been demonstrated that Ca 2ϩ sensitization mechanisms contribute to myogenic tone (28,30,49,50).…”

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confidence: 99%

Pregnancy attenuates uterine artery pressure-dependent vascular tone: role of PKC/ERK pathway

Xiao

Buchholz²,

Zhang³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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]i was significantly greater for pressure-induced contraction of NPUA than that of PUA. Inhibition of PKC by calphostin C significantly attenuated the pressure-induced vascular tone and eliminated the difference of myogenic responses between NPUA and PUA. In contrast, the MAPKK (MEK) inhibitor PD-098059 had no effect on NPUA but significantly enhanced myogenic responses of PUA. In the presence of PD-098059, there was no difference in pressure-induced myogenic responses between NPUA and PUA. The results suggest that pregnancy downregulates pressure-dependent myogenic tone of the uterine artery, which is partly due to increased MEK/ERK activity and decreased PKC signal pathway leading to a decrease in Ca 2ϩ sensitivity of myogenic mechanism in the uterine artery during pregnancy.sheep; protein kinase C; extracellular signal-regulated kinase PREGNANCY IS ASSOCIATED WITH a significant increase in uterine blood flow that optimizes the delivery of oxygen and substrates to the developing fetus via the placenta. The adaptations in the uterine circulation to pregnancy are complex and are mediated in part by enhanced vasodilation and vascular remodeling. Previous studies (3,47,54,57) have focused on the endothelial adaptation and have shown an increase in endothelial nitric oxide synthesis/release in the uterine artery during pregnancy. The adaptation of smooth muscle contractile mechanisms is less clear. Pressure-dependent myogenic contraction is an important physiological mechanism that regulates basal vascular tone and is a significant contributor to the modulation of blood flow (6, 21). Myogenic response has been found as either increased or decreased in uterine arteries of pregnant, compared with nonpregnant, rats, mice, and rabbits (5, 42, 51).Although arterial myogenic behavior has been studied intensively for decades, the mechanisms by which vascular smooth muscle cells respond to changes in intraluminal pressure are still not fully understood. Previous studies (17,29,37) indicated that myogenic tone was highly dependent on an elevation of intracellular free Ca 2ϩ concentration ([Ca 2ϩ ] i ). However, it has also been demonstrated that Ca 2ϩ sensitization mechanisms contribute to myogenic tone (28,30,49,50). Activation of various kinase cascades regulating Ca 2ϩ sensitivity of the contractile apparatus may modulate the level of arteriolar myogenic reactivity (8, 21). PKC has been proposed to play an important role in the regulation of basal vascular tone and arterial caliber, the major determinants of blood flow (6, 41, 44). Pressure-induced activation of PKC has been proposed to induce myogenic tone without additional increases in Ca 2ϩ concentrations or myosin light chain (MLC 20 ) phosphorylation (18, 31). Our recent studies have also demonstrated in ovine uterine arteries that activation of PKC causes sustained contractions in the absence of changes in [Ca 2ϩ ] i and MLC 20 phosphorylation levels (56) and that the PKC-mediated contraction is significantly attenuated in the uterine artery during pregnancy (...

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Protein kinase C potentiates stretch-induced cerebral artery tone by increasing intracellular sensitivity to Ca2+

Cited by 30 publications

References 12 publications

Pressure-induced myogenic tone and role of 20-HETE in mediating autoregulation of cerebral blood flow

Pressure-induced myogenic tone and role of 20-HETE in mediating autoregulation of cerebral blood flow

Selective Involvement of Serum Response Factor in Pressure-Induced Myogenic Tone in Resistance Arteries

Pregnancy attenuates uterine artery pressure-dependent vascular tone: role of PKC/ERK pathway

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