title: Hyperthyroidism enhances 5-HT-induced contraction of the rat pulmonary artery: role of calcium-activated chloride channel activation.
abstract: Experimentally-induced hyperthyroidism in rodents is associated with signs and symptoms of pulmonary hypertension. The main objective of the present study was to investigate the effect of thyroxine-induced pulmonary hypertension on the contractile response of the pulmonary artery to 5-HT and the possible underlying signaling pathway. 5-HT concentration-dependently contracted artery segments from control and thyroxine-treated rats with pD(2) values of 5.04 ± 0.19 and 5.34 ± 0.14, respectively. The maximum response was significantly greater in artery segments from thyroxine-treated rats. Neither BW 723C86 (5-HT(2B)-receptor agonist) nor CP 93129 (5-HT(1B)-receptor agonist) contracted ring segments of the pulmonary artery from control and thyroxine-treated rats at concentrations up to 10(-4)M. There was no significant difference in the level of expression of 5-HT(2A)-receptor protein between the two groups. Ketanserin (3 × 10(-8)M) produced a rightward shift of the concentration-response curve to 5-HT in both groups with equal potency (-logK(B) values were 8.1 ± 0.2 and 7.9 ± 0.1 in control and thyroxine-treated rats, respectively). Nifedipine (10(-6)M) inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. The calcium-activated chloride channel blocker, niflumic acid (10(-4)M) also inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. It was concluded that hyperthyroidism enhanced 5-HT-induced contractions of the rat pulmonary artery by a mechanism involving increased activity of calcium-activated chloride channels.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait. Oriowo@hsc.edu.kw
authors.forename: Mabayoje A
authors.initials: MA
authors.lastname: Oriowo
authors.forename: Elsie
authors.initials: E
authors.lastname: Oommen
authors.forename: Islam
authors.initials: I
authors.lastname: Khan
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D018118:Chloride Channels / Q000502:physiology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D006980:Hyperthyroidism / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D018490:Serotonin Agents / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013974:Thyroxine; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D018118:Chloride Channels; D044402:Receptor, Serotonin, 5-HT2A; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D012701:Serotonin; D013974:Thyroxine; D002118:Calcium