Human pulmonary arteries dilate to 20-HETE, an endogenous eicosanoid of lung tissue

Birks, Eric K.; Bousamra, Michael; Presberg, Kenneth W.; Marsh, James A.; Effros, Richard M.; Jacobs, Elizabeth R.

doi:10.1152/ajplung.1997.272.5.l823

Cited by 44 publications

(75 citation statements)

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“…This eicosanoid displays potent relaxing effects on HPAs, with IC 50 values in the submicromolar range (0.3 M) on either resting or active tone. To our knowledge, there are only a few publications concerning the relaxing effects of 20-HETE on precontracted rabbit and HPAs (2,14). Despite the fact that HT (n ϭ 16 experiments).…”

Section: Discussionmentioning

confidence: 99%

“…However, concomitant recordings of BK Ca channel activation in HPA smooth muscle cells have not been achieved yet. Nevertheless, it is of physiological interest to realize that 20-HETE displays relaxing effects on both HPA (2,14) and distal human bronchi (20).…”

Section: Cox Inhibition Affects 20-hete-dependent Relaxations Inmentioning

confidence: 99%

“…Our hypothesis is strengthened in that cytochrome P-450 4A ( -hydroxylase) protein levels were decreased in a model of shunt-induced PAH in piglets (23). Our understanding of the mechanisms involved in the pulmonary arterial dilation, and especially the 20-HETE-induced relaxation, thus appears to be of great interest in the new therapeutic development for PAH.Human and rabbit lung microsomes are able to metabolize arachidonic acid into 20-HETE, possibly via the activation of cytochrome P-450 4A, which is widely distributed in peripheral lung tissues, including small and large pulmonary arteries and airways as well (2,35). Such a wide distribution of the cytochrome P-450 4A raises the possibility that 20-HETE generated from nonvascular tissue could serve as an endogenous and paracrine modulator of pulmonary vascular tone (2, 35).…”

mentioning

confidence: 99%

“…Human and rabbit lung microsomes are able to metabolize arachidonic acid into 20-HETE, possibly via the activation of cytochrome P-450 4A, which is widely distributed in peripheral lung tissues, including small and large pulmonary arteries and airways as well (2,35). Such a wide distribution of the cytochrome P-450 4A raises the possibility that 20-HETE generated from nonvascular tissue could serve as an endogenous and paracrine modulator of pulmonary vascular tone (2, 35).…”

mentioning

confidence: 99%

“…Such a wide distribution of the cytochrome P-450 4A raises the possibility that 20-HETE generated from nonvascular tissue could serve as an endogenous and paracrine modulator of pulmonary vascular tone (2,35). Although arachidonic acid-induced relaxation in human pulmonary arteries (HPAs) involves cytochrome P-450-dependent metabolites and potassium channels (9), the precise molecular mode of action of 20-HETE remains to be ascertained.…”

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confidence: 99%

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Effects of ω-hydroxylase product on distal human pulmonary arteries

Morin¹,

Guibert²,

Sirois³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Morin C, Guibert C, Sirois M, Echave V, Gomes MM, Rousseau E. Effects of -hydroxylase product on distal human pulmonary arteries. Am J Physiol Heart Circ Physiol 294: H1435-H1443, 2008. First published January 18, 2008 doi:10.1152/ajpheart.01115.2007The aim of the present study was to provide a mechanistic insight into how 20-hydroxyeicosatetraenoic acid (20-HETE) relaxes distal human pulmonary arteries (HPAs). This compound is produced by -hydroxylase from free arachidonic acid. Tension measurements, performed on either fresh or 1 day-cultured pulmonary arteries, revealed that the contractile responses to 1 M 5-hydroxytryptamine were largely relaxed by 20-HETE in a concentration-dependent manner (0.01-10 M). Iberiotoxin pretreatments (10 nM) partially decreased 20-HETE-induced relaxations. However, 10 M indomethacin and 3 M SC-560 pretreatments significantly reduced the relaxations to 20-HETE in these tissues. The relaxing responses induced by the eicosanoid were likely related to a reduced Ca 2ϩ sensitivity of the myofilaments since free Ca 2ϩ concentration ([Ca 2ϩ ])-response curves performed on ␤-escin-permeabilized cultured explants were shifted toward higher [Ca 2ϩ ]. 20-HETE also abolished the tonic responses induced by phorbol-ester-dibutyrate (a PKC-sensitizing agent). Western blot analyses, using two specific primary antibodies against the PKC-potentiated inhibitory protein CPI-17 and its PKC-dependent phosphorylated isoform pCPI-17, confirmed that 20-HETE interferes with this intracellular process. We also investigated the effect of 20-HETE on the activation of Rho-kinase pathway-induced Ca 2ϩ sensitivity. The data demonstrated that 20-HETE decreased U-46619-induced Ca 2ϩ sensitivity on arteries. Hence, this observation was correlated with an increased staining of p116 Rip , a RhoA-binding protein. Together, these results strongly suggest that the 20-hydroxyarachidonic acid derivative is a potent modulator of tone in HPAs in vitro. 20-hydroxyeicosatetraenoic acid; calcium sensitivity; tension measurement PULMONARY ARTERY VASOCONSTRICTION and vascular remodeling greatly contribute to a sustained elevation of pulmonary vascular resistance and pulmonary arterial pressure in patients with pulmonary arterial hypertension (PAH), an often fatal hemodynamic abnormality (11). Pulmonary vasoconstriction is believed to be an early component of the pulmonary hypertensive process and has been attributed to an impaired production of vasodilators [nitric oxide (NO) and prostacyclin] and an increased production of vasoconstrictors (endothelin-1 and serotonin) (11). In that respect, vasodilators have some beneficial effects on PAH. Among various existing pulmonary arterial vasodilators, such as NO, sildenafil, and cGMP (24, 25), 20-hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P-450 4A metabolite of arachidonic acid, consistently dilates pulmonary arteries in several species, including humans (2). 20-HETE induces a relaxation in bovine pulmonary arteries, whereas it induces a contraction in bovine renal arte...

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Section: Discussionmentioning

confidence: 99%

Section: Cox Inhibition Affects 20-hete-dependent Relaxations Inmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of ω-hydroxylase product on distal human pulmonary arteries

Morin¹,

Guibert²,

Sirois³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Endothelial Cell Regulation of Pulmonary Vascular Tone, Inflammation, and Coagulation

Goldenberg

Kuebler

2015

Comprehensive Physiology

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The pulmonary endothelium represents a heterogeneous cell monolayer covering the luminal surface of the entire lung vasculature. As such, this cell layer lies at a critical interface between the blood, airways, and lung parenchyma, and must act as a selective barrier between these diverse compartments. Lung endothelial cells are able to produce and secrete mediators, display surface receptor, and cellular adhesion molecules, and metabolize circulating hormones to influence vasomotor tone, both local and systemic inflammation, and coagulation functions. In this review, we will explore the role of the pulmonary endothelium in each of these systems, highlighting key regulatory functions of the pulmonary endothelial cell, as well as novel aspects of the pulmonary endothelium in contrast to the systemic cell type. The interactions between pulmonary endothelial cells and both leukocytes and platelets will be discussed in detail, and wherever possible, elements of endothelial control over physiological and pathophysiological processes will be examined. C 2015 American Physiological Society.

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Lung Circulation

Suresh

Shimoda

2016

Comprehensive Physiology

104

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The circulation of the lung is unique both in volume and function. For example, it is the only organ with two circulations: the pulmonary circulation, the main function of which is gas exchange, and the bronchial circulation, a systemic vascular supply that provides oxygenated blood to the walls of the conducting airways, pulmonary arteries and veins. The pulmonary circulation accommodates the entire cardiac output, maintaining high blood flow at low intravascular arterial pressure. As compared with the systemic circulation, pulmonary arteries have thinner walls with much less vascular smooth muscle and a relative lack of basal tone. Factors controlling pulmonary blood flow include vascular structure, gravity, mechanical effects of breathing, and the influence of neural and humoral factors. Pulmonary vascular tone is also altered by hypoxia, which causes pulmonary vasoconstriction. If the hypoxic stimulus persists for a prolonged period, contraction is accompanied by remodeling of the vasculature, resulting in pulmonary hypertension. In addition, genetic and environmental factors can also confer susceptibility to development of pulmonary hypertension. Under normal conditions, the endothelium forms a tight barrier, actively regulating interstitial fluid homeostasis. Infection and inflammation compromise normal barrier homeostasis, resulting in increased permeability and edema formation. This article focuses on reviewing the basics of the lung circulation (pulmonary and bronchial), normal development and transition at birth and vasoregulation. Mechanisms contributing to pathological conditions in the pulmonary circulation, in particular when barrier function is disrupted and during development of pulmonary hypertension, will also be discussed.

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Human pulmonary arteries dilate to 20-HETE, an endogenous eicosanoid of lung tissue

Cited by 44 publications

References 0 publications

Effects of ω-hydroxylase product on distal human pulmonary arteries

Effects of ω-hydroxylase product on distal human pulmonary arteries

Endothelial Cell Regulation of Pulmonary Vascular Tone, Inflammation, and Coagulation

Lung Circulation

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