Cellular Mechanisms of Acrolein-Induced Alteration in Calcium Signaling in Airway Smooth Muscle

Hyvelin, Jean-Marc; Roux, Étienne; Prévost, Marie-Claude; Savineau, Jean‐Pierre; Marthan, Roger

doi:10.1006/taap.1999.8879

Cited by 35 publications

(26 citation statements)

References 24 publications

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“…The free ion concentrations of the physiological solutions were calculated with a computer program adapted from that by Fabiato (10) as previously described (19). In brief, we prepared activating solutions with different free Ca 2ϩ concentration by adding specified amounts of CaCl 2 to give a desired pCa.…”

Section: Methodsmentioning

confidence: 99%

“…Twenty minutes later, the bath solution was returned to control conditions. The response of a preparation to the intervention in these experiments was quantified as the difference between the average tension during minutes [15][16][17][18][19][20] after the switch to experimental conditions and the average steadystate control tension during the last 5 min before the switch. We took samples of the bathing fluid throughout all the experiments for the analysis of PCO2 and pH by using an automated blood-gas analyzer (model 278, Ciba Corning).…”

Section: Methodsmentioning

confidence: 99%

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Effect of changes in pH on wall tension in isolated rat pulmonary artery: role of the RhoA/Rho-kinase pathway

Hyvelin¹,

O’Connor²,

McLoughlin³

2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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Hyvelin, Jean-Marc, Clare O'Connor, and Paul McLoughlin. Effect of changes in pH on wall tension in isolated rat pulmonary artery: role of the RhoA/Rho-kinase pathway. Am J Physiol Lung Cell Mol Physiol 287: L673-L684, 2004. First published February 6, 2004 10.1152/ajplung.00331.2003 are resistant to the vasodilator effects of extracellular acidosis in systemic vessels; the mechanism underlying this difference between systemic and pulmonary circulations has not been elucidated. We hypothesized that RhoA/Rho-kinase-mediated Ca 2ϩ sensitization pathway played a greater role in tension development in pulmonary than in systemic vascular smooth muscle and that this pathway was insensitive to acidosis. In arterial rings contracted with the ␣ 1-agonist phenylephrine (PE), the Rho-kinase inhibitor Y-27632 (Յ3 M) induced greater relaxation in precontracted PA rings than in aortic rings. In PA rings stimulated by PE, the activation of RhoA was greater than in aorta. Normocapnic acidosis (NA) induced a smaller relaxation in precontracted PA than in aorta. However, in the presence of nifedipine and thapsigargin, when PE-induced contraction was predominantly mediated by Rho-kinase, the relaxant effect of NA was reduced and similar in both vessel types. Furthermore, in the presence of Y-27632, NA induced a greater relaxation in both PA and aorta, which was similar in both vessels. Finally, in ␣-toxin-permeabilized smooth muscle, PE-induced contraction at constant Ca 2ϩ activity was inhibited by Y-27632 and unaffected by acidosis. These results indicate that Ca 2ϩ sensitization induced by the RhoA/Rho-kinase pathway played a greater role in agonist-induced vascular smooth muscle contraction in PA than in aorta and that tension mediated by this pathway was insensitive to acidosis. The predominant role of the RhoA/Rho-kinase pathway in the pulmonary vasculature may account for the resistance of this circulation to the vasodilator effect of acidosis observed in the systemic circulation. vascular smooth muscle; acidosis; RhoA; calcium sensitization; Y-27632 NORMAL GAS EXCHANGE in the lung depends on the appropriate regulation of pulmonary blood flow to ensure matching of regional blood flow to ventilation to provide better gas exchanges. Hypoxic pulmonary vasoconstriction (HPV) is one of the main functional properties of the pulmonary circulation, which enables this matching. A second functional specialization seen in the pulmonary circulation is a resistance to the vasodilator effect of extracellular acidosis (5) in contrast to the potent vasodilator effect of this stimulus in the systemic circulation (1). Reduction in pH and elevation of PCO 2 in pulmonary arterial (PA) blood is observed in acute and chronic lung diseases. This resistance to acidosis plays an important role in ventilation-perfusion matching in the lung in such diseases, since a vasodilator response to hypercapnic acidosis would antagonize hypoxic vasoconstriction in poorly ventilated regions of the lung, thus diverting blood to these regions and impairing norma...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Effect of changes in pH on wall tension in isolated rat pulmonary artery: role of the RhoA/Rho-kinase pathway

Hyvelin¹,

O’Connor²,

McLoughlin³

2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In human bronchial smooth muscle, for example, RyR, though present and functional, do not participate in the acetylcholine-induced Ca 2+ response (Hyvelin et al, 2000a). (Gunter et al, 2000;Roux et al, 2004 (Bergner et al, 2002;Hyvelin et al, 2000b;Kajita et al, 1993;Liu et al, 1996). Changes in [Ca 2+ ] i are not uniform within the cytosol, and studies have evidenced the role of local change in Ca 2+ signalling (Prakash et al, 2000).…”

Section: Camentioning

confidence: 99%

Role of Protein Kinase Network in Excitation-Contraction Coupling in Smooth Muscle Cell

Roux¹,

Mbikou²,

Fajmut³

2012

Protein Kinases

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“…For example, each may induce hypercontraction by: (1) Ca 2+ overload (Hyvelin et al, 2000), (2) fixation of myofibrillar proteins (acrolein is an excellent fixative) (Murata et al, 1985), (3) rapid depletion of ATP levels and ATP production (Biagini et al, 1990), and (4) rapid depletion of reduced GSH level (Awasthi and Boor, 1994) (vide supra). Although these mechanisms are not mutually exclusive, our data implicate calcium overload in AA-induced (or acrolein-induced) hypercontraction.…”

Section: Acrolein Generator Induces Calcium Overload-a Working Hypothmentioning

confidence: 99%

“…In our study, calcium repletion rapidly increased tension in AA-exposed blood vessels and thus extracellular calcium entry appears necessary for both hyper-contraction and sustained tension in IMA. Similarly, acrolein exposure stimulates airway smooth muscle hypercontractility and calcium entry ex vivo (Ben Jebria et al, 1995;Hyvelin et al, 2000).…”

Section: Acrolein Generator Induces Calcium Overload-a Working Hypothmentioning

confidence: 99%

Acrolein generation stimulates hypercontraction in isolated human blood vessels

Conklin

Bhatnagar

Cowley

et al. 2006

Toxicology and Applied Pharmacology

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Increased risk of vasospasm, a spontaneous hyperconstriction, is associated with atherosclerosis, cigarette smoking, and hypertension-all conditions involving oxidative stress, lipid peroxidation, and inflammation. To test the role of the lipid peroxidation-and inflammation-derived aldehyde, acrolein, in human vasospasm, we developed an ex vivo model using human coronary artery bypass graft (CABG) blood vessels and a demonstrated acrolein precursor, allylamine. Allylamine induces hypercontraction in isolated rat coronary artery in a semicarbazide-sensitive amine oxidase activity (SSAO) dependent manner. Isolated human CABG blood vessels (internal mammary artery, radial artery, saphenous vein) were used to determine: (1) vessel responses and sensitivity to acrolein, allylamine, and H 2 O 2 exposure (1 μM-1 mM), (2) SSAO dependence of allylamine-induced effects using SSAO inhibitors (semicarbazide, 1 mM; MDL 72274-E, active isomer; MDL 72274-Z, inactive isomer; 100 μM), (3) the vasoactive effects of two other SSAO amine substrates, benzylamine and methylamine, and (4) the contribution of extracellular Ca 2+ to hypercontraction. Acrolein or allylamine but not H 2 O 2 , benzylamine, or methylamine stimulated spontaneous and pharmacologically intractable hypercontraction in CABG blood vessels that was similar to clinical vasospasm. Allylamine-induced hypercontraction and blood vessel SSAO activity were abolished by pretreatment with semicarbazide or MDL 72274-E but not by MDL 72274-Z. Allylamine-induced hypercontraction also was significantly attenuated in Ca 2+ -free buffer. In isolated aorta of spontaneously hypertensive rat, allylamine-induced an SSAOdependent contraction and enhanced norepinephrine sensitivity but not in Sprague-Dawley rat aorta. We conclude that acrolein generation in the blood vessel wall increases human susceptibility to vasospasm, an event that is enhanced in hypertension.

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Cellular Mechanisms of Acrolein-Induced Alteration in Calcium Signaling in Airway Smooth Muscle

Cited by 35 publications

References 24 publications

Effect of changes in pH on wall tension in isolated rat pulmonary artery: role of the RhoA/Rho-kinase pathway

Effect of changes in pH on wall tension in isolated rat pulmonary artery: role of the RhoA/Rho-kinase pathway

Role of Protein Kinase Network in Excitation-Contraction Coupling in Smooth Muscle Cell

Acrolein generation stimulates hypercontraction in isolated human blood vessels

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