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The role of Ca L in sheep pulmonary arteries is altered by chronic hypoxia and postnatal maturation
Author(s) -
Vemulakonda Srilakshmi,
Papamatheakis Demosthenes G,
Blood Quintin,
Merritt Travis,
Longo Lawrence D.,
Wilson Sean M
Publication year - 2010
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.24.1_supplement.1061.6
Subject(s) - diltiazem , fetus , verapamil , contraction (grammar) , nifedipine , endocrinology , medicine , hypoxia (environmental) , chemistry , pulmonary hypertension , calcium , biology , oxygen , pregnancy , organic chemistry , genetics
L‐type Ca 2+ channels (Ca L ) are important to electro‐ and pharmaco ‐mechanical coupling in pulmonary arteries (PA). Evidence indicates the role of Ca L to PA contraction is potentially reduced by chronic hypoxia (CH) but increased after birth. We tested the hypotheses that these couplings are blunted by CH and accentuated following birth by examining contraction in PA rings isolated from near term sheep fetuses (~140 days) and adult ewes maintained under normoxic (300 m) or CH conditions (3801 m) for 100+ days. PA rings were depolarized with cumulative [K + ] doses, from 5 to 125 mM or stimulated with 10 μM serotonin (5‐HT). The estimated V 1/2 for K + ‐induced contraction was ~ 10 mV more negative in PA from normoxic ewes relative to normoxic fetuses or CH fetuses or ewes. Ca L inhibition with 10 μM verapamil (VER), diltiazem (DIL) or nifedipine (NIF) reduced, but did not ablate, K + ‐dependent contraction. NIF reduced 5‐HT elicited tension more significantly in rings from normoxic ewes relative to fetuses or CH ewes and fetuses. VER inhibited 5‐HT elicited tension more than DIL or NIF. Overall, electromechanical coupling appears restrained before birth and by CH and non‐Ca L ‐related pathways contribute to this coupling process. VER possibly blocks non‐Ca L pathways during pharmacomechanical but not electromechanical coupling, which may provide insights regarding its therapeutic actions. NIH P01HD031226, R01HD003807 (LDL)