Coronary Artery Spasm Does Not Depend on the Intracellular Calcium Store but Is Substantially Mediated by the Protein Kinase C–Mediated Pathway in a Swine Model With Interleukin-1β In Vivo

Kadokami, Toshiaki; Shimokawa, Hiroaki; Ito, Akira; Takayanagi, T; Egashira, Kensuke; Takeshita, Akira

doi:10.1161/01.cir.94.2.190

Cited by 42 publications

(38 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the sustained phase, Ca 2ϩ influx from extracellular space is central and involves Rho-kinase-mediated Ca 2ϩ sensitization. Although both pathways have been postulated to play a role in coronary vasospasm, 17,18 our data indicate that Rho-kinase is the dominant factor in thromboxane receptor-mediated contraction.…”

Section: Discussionmentioning

confidence: 64%

“…The evidence for the operation of these pathways of Ca 2ϩ sensitization in vivo and for their clinical significance has been inferred largely from studies based on contractility alone. 17,18 Therefore, we measured the time course of [Ca 2ϩ ] i and isometric force simultaneously in an intact artery in response to a single addition of U46619. We report that U46619-induced contraction is characterized by two distinct phases of Ca 2ϩ sensitization, having either PKC-mediated or Rhokinase-mediated mechanisms, with the latter dominant in the steady state.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Distinct Pathways of Ca ²⁺ Sensitization in Porcine Coronary Artery

Nobe

Rutgeerts

2001

Circulation Research

View full text Add to dashboard Cite

Abstract-Alterations of the Ca 2ϩ sensitivity of contraction have been reported for porcine coronary artery, but the mechanisms are not clearly understood. We investigated the mechanism(s) of Ca 2ϩ sensitization in response to the thromboxane A 2 analogue (U46619). Our hypothesis is that different mechanisms of Ca 2ϩ sensitization could be distinguished by their distinct time courses. Therefore, we measured the time course of [Ca 2ϩ ] i and isometric force simultaneously in an intact artery after a single addition of U46619. The initial transient phase was associated with Ca 2ϩ release from the sarcoplasmic reticulum, whereas the maintained phase was associated with Ca 2ϩ influx. Two distinct types of Ca 2ϩ sensitization characterized these phases with either protein kinase C (PKC)-mediated or Rho-kinasemediated mechanisms. Their effects were quite distinct on the basis of the time courses over which the sensitization was effective. PKC inhibition (1 mol/L calphostin C) had a much greater effect in the initial phase, diminishing the size of the transient and prolonging the rise in force and the decline in [Ca 2ϩ ] i . There were limited effects on the sustained force. Rho-kinase inhibition (10 mol/L Y27632), in contrast, nearly abolished the sustained force but had a lesser effect on the transient phase. Neither inhibitor had any effect on the force versus [Ca 2ϩ ] i relations for KCl contractures. Our evidence suggests that both PKC-mediated and Rho-kinase-mediated Ca 2ϩ sensitizations are present in coronary arteries, but the latter is dominant in thromboxane A 2 receptor-mediated contraction.

show abstract

Section: Discussionmentioning

confidence: 64%

mentioning

confidence: 99%

Distinct Pathways of Ca ²⁺ Sensitization in Porcine Coronary Artery

Nobe

Rutgeerts

2001

Circulation Research

View full text Add to dashboard Cite

show abstract

“…PKC activators were indeed able to favor, whereas PKC inhibitors prevented, CAS induction by serotonin and histamine. 42 More recently, another experimental model of CAS characterized by VSMC hyperreactivity has been developed in knockout mice for SUR-2, a component of the ATPdependent K ϩ channel. 43 In this model, spontaneous spasm occurred in completely normal coronary arteries and caused premature sudden death.…”

Section: Primary Vsmc Hyperreactivitymentioning

confidence: 99%

“…Il apparaît, en effet, que les activateurs de la PKC favorisent l'induction de SC par la sérotonine et l'histamine, alors que les inhibiteurs de cette enzyme la préviennent. 42 Plus récemment, un autre modèle expérimental de SC se caractérisant par une hyperréactivité des CMLV a été conçu en employant des souris privées de SUR-2, qui est une sousunité constitutive des canaux potassiques ATP-dépendants. 43 Dans ce modèle, des artères coronaires totalement normales ont été le siège de spasmes spontanés qui ont entraîné la mort subite prématurée des animaux.…”

Section: L'hyperréactivité Primitive Des CMLVunclassified

Mechanisms of Coronary Artery Spasm

2011

View full text Add to dashboard Cite

“…Although the influence of PKC on vascular tone has been investigated in various vascular beds, studies have thus far yielded conflicting results with regard to the physiological significance of this pathway (Kadokami et al, 1996;Chrissobolis and Sobey, 2001;Woodsome et al, 2001). Furthermore, the relative contributions of rho-kinase and PKC to vascular contraction and whether their roles vary between large and small blood vessels within a vascular bed are not well understood.…”

mentioning

confidence: 99%

Segmental Differences in the Roles of Rho-Kinase and Protein Kinase C in Mediating Vasoconstriction

Budzyn

Paull²,

Marley³

et al. 2006

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Rho-kinase and protein kinase C (PKC) have each been reported to mediate vasoconstriction via calcium sensitization. However, the relative contributions of these two kinases to vascular contraction, and whether their roles vary between large and small arteries, are largely unknown. We therefore assessed the relative roles of rho-kinase and PKC in mediating vasoconstriction in arteries from three segments of the aortic and mesenteric vasculature. We studied contractile responses of rat isolated thoracic aorta (diameter Ϸ2 mm), superior mesenteric artery (SMA; Ϸ1.5 mm), and second order branches of the superior mesenteric artery (BMA; Ϸ300 m). The roles of rho-kinase and PKC in mediating contractile responses to phenylephrine, 9,11-dideoxy-9,11-methanoepoxy prostaglandin F 2␣ (U46619), and KCl were assessed by using the rhokinase inhibitor R- Cotreatment with Y-27632 and Ro 31-8220 markedly attenuated contractile responses to phenylephrine and KCl in all vessels, but it had only a moderate inhibitory effect on responses to U46619 in aorta and SMA. Thus, contractile responses of the larger arteries can involve both rho-kinase and PKC to varying degrees. Conversely, contractile responses of small mesenteric resistance arteries seem to be mediated exclusively by PKC, with no apparent role for rho-kinase.

show abstract

Coronary Artery Spasm Does Not Depend on the Intracellular Calcium Store but Is Substantially Mediated by the Protein Kinase C–Mediated Pathway in a Swine Model With Interleukin-1β In Vivo

Cited by 42 publications

References 26 publications

Distinct Pathways of Ca ²⁺ Sensitization in Porcine Coronary Artery

Distinct Pathways of Ca ²⁺ Sensitization in Porcine Coronary Artery

Mechanisms of Coronary Artery Spasm

Segmental Differences in the Roles of Rho-Kinase and Protein Kinase C in Mediating Vasoconstriction

Contact Info

Product

Resources

About

Coronary Artery Spasm Does Not Depend on the Intracellular Calcium Store but Is Substantially Mediated by the Protein Kinase C–Mediated Pathway in a Swine Model With Interleukin-1β In Vivo

Cited by 42 publications

References 26 publications

Distinct Pathways of Ca 2+ Sensitization in Porcine Coronary Artery

Distinct Pathways of Ca 2+ Sensitization in Porcine Coronary Artery

Mechanisms of Coronary Artery Spasm

Segmental Differences in the Roles of Rho-Kinase and Protein Kinase C in Mediating Vasoconstriction

Contact Info

Product

Resources

About

Distinct Pathways of Ca ²⁺ Sensitization in Porcine Coronary Artery

Distinct Pathways of Ca ²⁺ Sensitization in Porcine Coronary Artery