The role of tyrosine kinase in hypoxic constriction of sheep pulmonary artery rings

Uzun, Orhan; Demiryürek, A. Tuncay; Kanzik, I

doi:10.1016/s0014-2999(98)00592-5

Cited by 18 publications

(9 citation statements)

References 32 publications

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“…Whether any of these responses are linked to Rho activation, with or without the involvement of G-proteins, cGMP pathway, GDI, GAP, or GEF, also needs further investigation. HPV has been shown to be inhibited by tyrosine kinase inhibitors (41) and PKC inhibitors (42). Whether these effects are mediated through the inhibition of Rho activation will also require further investigation.…”

Section: Discussionmentioning

confidence: 99%

Rho-Kinase Activation Is Involved in Hypoxia-Induced Pulmonary Vasoconstriction

Wang

Jin

Ganguli

et al. 2001

Am J Respir Cell Mol Biol

125

106

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Rho-associated serine/threonine kinase (Rho-kinase) is a downstream effector of small GTPase RhoA that has recently been shown to play an important role in regulating smooth muscle contraction. The present study investigated the role of Rho/ Rho-kinase in hypoxia-induced pulmonary vasoconstriction (HPV). Small pulmonary resistance vessels and cultured pulmonary arterial smooth muscle cells (PASMCs) from the rat were used. PASMCs exposed to hypoxia (PO(2) = 26 +/- 2 mm Hg) showed a significant increase in Rho-kinase activity. Exposure to hypoxia for 20, 40, 60, 90, and 120 min also resulted in a significant increase in myosin light chain (MLC) phosphorylation at all time points in PASMCs. Hypoxia-induced MLC phosphorylation was inhibited by Y-27632 (a Rho-kinase inhibitor), exoenzyme C3 (a specific Rho inhibitor), or toxin B (an inhibitor for Rho proteins). In addition, hypoxia-induced Rho-kinase activation was blocked by C3 and toxin B. Small rat intrapulmonary arterial rings, which were made hypoxic (PO(2) = 30 +/- 3 mm Hg), showed a slow sustained contraction, and Y-27632 caused a significant relaxation during the sustained phase of HPV in a concentration-dependent manner. In summary, the data show that Rho-kinase is activated by hypoxia in PASMCs, and Rho/Rho-kinase is functionally linked to hypoxia-induced MLC phosphorylation and plays a role in the sustained phase of HPV.

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Section: Discussionmentioning

confidence: 99%

Rho-Kinase Activation Is Involved in Hypoxia-Induced Pulmonary Vasoconstriction

Wang

Jin

Ganguli

et al. 2001

Am J Respir Cell Mol Biol

125

106

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“…Relationships between the level of hypoxia and magnitude of phase 1 vasoconstriction in prestimulated rat proximal pulmonary arteries suggested that the response began to occur at ϳ8% O 2 , and was half-maximum at ϳ3% O 2 and maximum at 0% O 2 (1651,1652,1691). These O 2 concentrations were shifted to higher values when the intensity of prestimulation was increased (1652) or when measurements were made in a rat strain more responsive to hypoxia (1691 656,799,814,900,903,935,991,1043,1045,1131,1151,1413,1430,1651,1652,1691,1896,1961,1976,2018,2089,2185). Moreover, substantial data suggested that the endothelium dependence of phase 1 was caused by an hypoxia-induced decrease in endothelial NO production, leading to smooth muscle contraction (506, 656,814,903,934,935,991,1151,1413,1430,1691,1896,1976,2018).…”

Section: Pulmonary Arteriesmentioning

confidence: 98%

Hypoxic Pulmonary Vasoconstriction

Sylvester

Shimoda

Aaronson

et al. 2012

Physiological Reviews

599

621

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It has been known for more than 60 years, and suspected for over 100, that alveolar hypoxia causes pulmonary vasoconstriction by means of mechanisms local to the lung. For the last 20 years, it has been clear that the essential sensor, transduction, and effector mechanisms responsible for hypoxic pulmonary vasoconstriction (HPV) reside in the pulmonary arterial smooth muscle cell. The main focus of this review is the cellular and molecular work performed to clarify these intrinsic mechanisms and to determine how they are facilitated and inhibited by the extrinsic influences of other cells. Because the interaction of intrinsic and extrinsic mechanisms is likely to shape expression of HPV in vivo, we relate results obtained in cells to HPV in more intact preparations, such as intact and isolated lungs and isolated pulmonary vessels. Finally, we evaluate evidence regarding the contribution of HPV to the physiological and pathophysiological processes involved in the transition from fetal to neonatal life, pulmonary gas exchange, high-altitude pulmonary edema, and pulmonary hypertension. Although understanding of HPV has advanced significantly, major areas of ignorance and uncertainty await resolution.

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“…Isometric contractions were recorded continuously with an amplifier system (Tümel, I˙zmir, Turkey) on a computer, using the Labsys computer program. Arterial rings were equilibrated in Krebs-Henseleit solution gassed with room air for 1 h at their optimum resting force (3 g) [9]. The isometric contractions were calculated as force developed per cross-sectional area as presented previously [9,10].…”

Section: Methodsmentioning

confidence: 99%

“…Arterial rings were equilibrated in Krebs-Henseleit solution gassed with room air for 1 h at their optimum resting force (3 g) [9]. The isometric contractions were calculated as force developed per cross-sectional area as presented previously [9,10]. The artery rings were exposed repeatedly, generally three times, to 20 mmol/l KCl until two consecutive identical responses were observed before the start of the experimental protocol.…”

Section: Methodsmentioning

confidence: 99%

Role of G<sub>S</sub> Proteins in Hypoxic Constriction of Sheep Pulmonary Artery Rings

Uzun

Demiryürek²,

Kanzik³

2002

Pharmacology

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The introduction of hypoxia is well known to cause contraction of pulmonary artery rings in vitro. Despite intensive studies, the cellular mechanisms of hypoxic pulmonary vasoconstriction are still not well defined. In this study, we aimed to determine the contribution of G_S proteins in hypoxia-induced vasoconstriction in large-diameter sheep pulmonary arteries using cholera toxin (CT). Hypoxia caused further contractions in serotonin but not in NaF-precontracted pulmonary artery rings. However, hypoxic vasoconstriction due to lowering of pO₂ from 97 to 5 mm Hg was totally abolished by preincubation with CT in serotonin-precontracted arteries. These preliminary results indicate that signal transduction mediated by G_s proteins may be an important mechanism in the hypoxic vasoconstriction of isolated pulmonary arteries of sheep.

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The role of tyrosine kinase in hypoxic constriction of sheep pulmonary artery rings

Cited by 18 publications

References 32 publications

Rho-Kinase Activation Is Involved in Hypoxia-Induced Pulmonary Vasoconstriction

Rho-Kinase Activation Is Involved in Hypoxia-Induced Pulmonary Vasoconstriction

Hypoxic Pulmonary Vasoconstriction

Role of G<sub>S</sub> Proteins in Hypoxic Constriction of Sheep Pulmonary Artery Rings

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