Antenatal chronic hypoxia and L‐type Ca 2+ ‐dependent contractility of pulmonary arteries from fetal sheep (1089.6)

Recently we and others have shown that K + ‐depolarization induced pulmonary arterial (PA) contraction is due to the combined activation of L‐type Ca 2+ channels (Ca L ) and Rho kinase (ROK). In fetal sheep we demonstrated that Ca L inhibition with nifedipine (NIF) reduced 125 mM K + ‐mediated contraction up to about one‐half, with ROK contributing the remainder, and that the relationship between these two pathways was preserved following antenatal chronic hypoxia (CH). To better define the relationship between these pathways and the impact of antenatal CH, we tested the hypothesis that direct activation of Ca L would elicit a NIF sensitive contraction and this contraction would be preserved following antenatal CH. This was examined using wire‐myography approaches on small diameter PA isolated from normoxic (~700 m) and antenatal CH (3,801 m, for >100 days) late gestation fetal sheep. Our results show that direct activation of Ca L with 10 μM FPL 64176 (FPL) elicited a contraction that was approximately 80‐125% of the maximum K + ‐induced depolarization (T Kmax ) in normoxic and hypoxic PA. In both normoxic and hypoxic PA 10 μM NIF reduced FPL‐induced contraction back to baseline. These data illustrate that NIF‐sensitive Ca L ‐dependent contraction is preserved following antenatal CH and when compared to our previous work that direct Ca L activation causes fetal PA constriction in a distinct way compared to K + ‐depolarization. Grant Funding Source : Supported by NSF MRI 0923559, NIH HD‐069746, P01HD031226, R01HD003807