title: Prostaglandins in action indispensable roles of cyclooxygenase-1 and -2 in endothelium-dependent contractions.
abstract: Endothelium regulates local vascular tone by means of releasing relaxing and contracting factors, of which the latter have been found to be elevated in vascular pathogenesis of hypertension, diabetes, hypercholesterolemia, and aging. Endothelium-derived contracting factors (EDCFs) are mainly metabolites of arachidonic acid generated by cyclooxygenase (COX), as vasodilatations in patients with hypertension, metabolic diseases, or advancing age are improved by acute treatment with COX inhibitor indomethacin. COX is presented in two isoforms, COX-1 and COX-2, with the former regarded as constitutive and the latter mainly expressed upon induction. Experiments with animal models of vascular dysfunctions, however, reveal that both isoforms have similar capacity to participate in endothelium-dependent contractions, with augmented expression and activity. COX-derived prostaglandin (PG) H(2), PGF(2α), PGE(2), prostacyclin (PGI(2)), and thromboxane A(2) (TxA(2)) are the proposed EDCFs that mediate endothelium-dependent contractions via the activation of thromboxane-prostanoid (TP) receptor in various vascular beds from different species. Although COX inhibition seems to be a possible strategy in combating COX-associated vascular complications, the incidence of adverse cardiovascular effects of Vioxx has greatly antagonized this concept. Further review of COX inhibitors is required, especially toward the selectivity of coxibs and whether it directly inhibits prostacyclin synthase activity. Meanwhile, TP receptor antagonism may emerge as a therapeutic alternative to reverse prostanoid-mediated vascular dysregulations.
authors.affiliation: Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Siu Ling
authors.initials: SL
authors.lastname: Wong
authors.forename: Wing Tak
authors.initials: WT
authors.lastname: Wong
authors.forename: Xiao Yu
authors.initials: XY
authors.lastname: Tian
authors.forename: Chi Wai
authors.initials: CW
authors.lastname: Lau
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D051545:Cyclooxygenase 1 / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D011453:Prostaglandins / Q000494:pharmacology / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2