Predominant role of vasoconstrictors over dilatators derived from arachidonic acid in hypoxic pulmonary vasoconstriction

Han,Yeshan; Yan,Gaoliang; Wang,Qingjie; Ma,Gengshan; Tang,Chengchun; Gu,Yuchun; Li,Li; Zhao,Jianzhong

doi:10.3892/mmr.2013.1645

Predominant role of vasoconstrictors over dilatators derived from arachidonic acid in hypoxic pulmonary vasoconstriction

Authors:
- Yeshan Han
- Gaoliang Yan
- Qingjie Wang
- Gengshan Ma
- Chengchun Tang
- Yuchun Gu
- Li Li
- Jianzhong Zhao
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Affiliations: Department of Anesthesiology, Changzhou No. 2 People's Hospital, Changzhou, Jiangsu 213003, P.R. China , Department of Cardiology, Zhongda Hospital of Southeast University Medical School, Nanjing, Jiangsu 210009, P.R. China, Institute of Molecular Medicine, Peking University, Beijing 100871, P.R. China, Department of Cardiology, Changzhou No. 2 People's Hospital, Changzhou, Jiangsu 213003, P.R. China
Published online on: August 19, 2013 https://doi.org/10.3892/mmr.2013.1645
Pages: 1263-1271

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Abstract

Prostanoids derived from arachidonic acid (AA) have been shown to play a permissive role in the regulation of vascular tone and wall tension. Conventionally, epoxyeicosatrienoic acids (EETs) and prostacyclin have been considered as dilatators, whereas thromboxane (TX) and hydroxyeicosatetraenoic acid (HETE) were considered as vasoconstrictors. However, the role of these prostanoids in the mediation of acute hypoxic pulmonary vasoconstriction is not yet clearly understood. In the present study, the role of prostanoids in the acute hypoxic response in rat isolated intrapulmonary arteries (IPAs) was investigated. Exogenous AA directly caused vasoconstriction, but exerted a significant inhibition on hypoxic vasoconstriction. The vasoconstriction by AA was mediated by the endothelium. AA metabolites from lipoxygenase (LOX) had no effect on vascular tone or hypoxic vasoconstriction. Consistent results from the blockage of cytochrome P450 (CYP) or CYP epoxide hydrolase showed that HETE contributed to endothelium‑independent hypoxic vasoconstriction. EET via epoxygenase exerted no effect on 80 mM KPSS‑induced vessel contraction or hypoxic vasoconstriction. In addition, prostacyclin also failed to inhibit hypoxic pulmonary vasoconstriction (HPV). However, blockage of thromboxane A2/prostanoid (TP) receptors almost eliminated hypoxic vasoconstriction, suggesting the primary role of TP receptors in the regulation of the hypoxic response in rat IPAs. In conclusion, the current data indicate the predominant role of vasoconstrictors instead of dilatators in mediating HPV. These data also highlight a pivotal role for voltage‑independent Ca2+ entry in pulmonary hypoxic response and suggest that modulation of these channels by prostanoids underlies their regulatory mechanisms.

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