title: Predominant role of vasoconstrictors over dilatators derived from arachidonic acid in hypoxic pulmonary vasoconstriction.
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.
authors: Department of Anesthesiology, Changzhou No. 2 People's Hospital, Changzhou, Jiangsu 213003, P.R. China.
authors: Yeshan
authors: Y
authors: Han
authors: Gaoliang
authors: G
authors: Yan
authors: Qingjie
authors: Q
authors: Wang
authors: Gengshan
authors: G
authors: Ma
authors: Chengchun
authors: C
authors: Tang
authors: Yuchun
authors: Y
authors: Gu
authors: Li
authors: L
authors: Li
authors: Jianzhong
authors: J
authors: Zhao
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002208:Caproates / Q000494:pharmacology; D002248:Carbon Monoxide / Q000494:pharmacology; D015687:Cell Hypoxia; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013931:Thromboxanes / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
chemical_list: C121755:6-(2-propargyloxyphenyl)hexanoic acid; D001095:Arachidonic Acids; D002208:Caproates; D065607:Cytochrome P-450 Enzyme Inhibitors; D013931:Thromboxanes; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D014700:Verapamil; D011464:Epoprostenol