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5‐HT2A receptor mediated contractility of Ovine pulmonary arteries: Effects of maturation and chronic hypoxia
Author(s) -
Goyal Ravi,
Loftin Matthew,
Derrick Allison,
Nguyen Dan,
Pearce William J,
Longo Lawrence D,
Wilson Sean M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1150.4
Subject(s) - contractility , ketanserin , endocrinology , medicine , potency , hypoxia (environmental) , receptor antagonist , fetus , biology , receptor , myocyte , antagonist , electrical impedance myography , serotonin , chemistry , 5 ht receptor , in vitro , vasodilation , pregnancy , biochemistry , genetics , organic chemistry , oxygen
Serotonin (5‐HT) signaling plays important roles in pulmonary vascular contractility and development. Several studies illustrate that 5‐HT mediated pulmonary arterial (PA) contractility adapts with development in sheep and rat and in response to chronic hypoxic (CH) stress in the rat. Our studies show that 5‐HT induced Ca 2+ elevations in fewer PA myocytes from fetal relative to adult sheep suggesting there may be increases in receptor expression associated with maturation. Using wire myography approaches, the present study tested the hypothesis that CH and maturation increase the potency as well as efficacy of 5‐HT‐mediated PA contractility in sheep. The results show the EC 50 to 5‐HT was unchanged with maturation in PA from normoxic sheep. However, the potency to 5‐HT was reduced with CH in fetus and increased in adult. The tension developed by 10 μM 5‐HT increased with maturation but not CH and no differences were observed when normalized to the tension due to 125 mM KCl. Moreover, in all groups the contractility to 1 μM 5‐HT was completely abolished by 100 nM Ketanserin, a selective 5‐HT 2A antagonist. In conclusion, based on this and our previous studies the changes in 5‐HT efficacy and potency with maturation and CH are most likely due to altered receptor number, second messenger coupling or phenotypic alterations in PA myocyte function. (Support from NIH, Sigma Xi, and UM)