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Chronic hypoxia and the influence of maturation on serotonergic contractility in Ovine pulmonary arteries
Author(s) -
Goyal Ravi,
Pearce William J,
Longo Lawrence D,
Wilson Sean M
Publication year - 2007
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.21.6.a1339-a
Subject(s) - contractility , nifedipine , medicine , hypoxia (environmental) , electrical impedance myography , pulmonary hypertension , fetus , endocrinology , serotonergic , pulmonary artery , serotonin , vasodilation , cardiology , chemistry , calcium , biology , receptor , pregnancy , organic chemistry , oxygen , genetics
Serotonin (5‐hydroxytryptamine, 5‐HT) is a potent biogenic amine in the pulmonary vasculature where it causes arterial contractility and vascular remodeling. 5‐HT as well as chronic hypoxia (CH) are risk factors in the development of pulmonary arterial hypertension and persistent pulmonary hypertension of the newborn. We therefore tested the hypothesis that there are differences in 5‐HT mediated contractility in pulmonary arteries (PA) of CH fetal and adult sheep using wire myography of fourth order endothelium disrupted arterial segments (~ 250 μm). The results show that adult PA were far more responsive to 5‐HT than those of fetal. Adult PA responded to lower concentrations of 5‐HT than fetal with almost a half a log‐unit difference in the EC 50 . The roles of L‐type calcium channels (Ca L ), non selective cation channels (NSCC) and IP 3 receptors were then evaluated by antagonizing 5‐HT preconstricted arterial segments with 10 μM nifedipine, 50 μM SKF96365 , and 50 μM 2‐APB in an additive manner. The contribution of Ca L and NSCCs was greater in adult PA (P < 0.05) while the component insensitive to the antagonist‐cocktail was greater in fetal PA (P<0.001) as determined by one‐way ANOVA. In comparison, the contribution of IP 3 pathways did not change with maturation. We are investigating whether the differences in 5‐HT contractility are due solely to maturation or if there is an interactive effect of CH. Supported by NIH and UM.