Chronic hypoxia increases the importance of BKCa channels to bradykinin‐mediated pulmonary vasodilation in fetal sheep (1089.18)

Abstract

Bradykinin‐induced activation of the pulmonary endothelium triggers a nitric oxide (NO)‐ signaling pathway. Pathway activation causes vasodilation and is critical to the fetal transition at birth, which regulates lung blood flow and 02 uptake. Part of this vasodilation process includes stimulation of large‐conductance K+ (BKCa) channels that hyperpolarizes the plasma membrane of myocytes. Intrauterine chronic hypoxia (CH) may reduce vasodilation in the fetal transition, and contribute to the development of pulmonary hypertension of the newborn. Thus, we examined the effects of maturation and LTH on the role of BKCa channels during bradykinin‐induced vasodilation by performing wire‐myography on pulmonary arteries (PA) isolated from fetal or adult sheep that lived in normoxia at low altitude or from sheep that lived in CH at high altitude (3,801 m) for >100 days. BKCa channels were blocked with 1mM tetraethylammonium (TEA). Interestingly, bradykinin relaxed fetal hypoxic vessels more extensively than fetal normoxic vessels, indicating a compensatory response due to CH. TEA only reduced bradykinin‐induced vasodilation in the fetal hypoxic vessels. Overall, these results suggest that LTH amplifies the importance of BKCa channels to bradykinin‐induced vasodilation in fetal sheep, and the BKCa channel has the potential for being a future therapeutic avenue to treat pulmonary hypertension of the newborn.Grant Funding Source: Supported by NSF MRI 0923559, NIH HD069746,P01HD031226, R01HD003807,5P20 MD‐006988, LLUSOM