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Bradykinin‐induced pulmonary vasorelaxation is modified by long term hypoxia and postnatal maturation in sheep
Author(s) -
BlumJohnston Carla,
Blood Quintin,
Wee Chelsea,
Wilson Rachael,
Blood Arlin B,
Longo Lawrence D,
Wilson Sean
Publication year - 2013
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.27.1_supplement.1140.7
Subject(s) - bradykinin , hypoxia (environmental) , prostacyclin , nitric oxide , fetus , enos , pulmonary hypertension , endocrinology , medicine , vasodilation , chemistry , receptor , biology , nitric oxide synthase , oxygen , pregnancy , organic chemistry , genetics
Endothelial activation is critical to pulmonary vasorelaxation during the fetal transition. Bradykinin (BK) relaxes vessels through endothelial‐induced nitric oxide (NO) and prostacyclin (PGI 2 ) dependent signaling pathways. Intrauterine long term hypoxia (LTH) can stunt vasorelaxation in the fetal transition and cause pulmonary hypertension of the newborn. We therefore tested the hypothesis that LTH impairs maturation of BK‐mediated vasorelaxation by performing wire‐myography on pulmonary arteries (PA) isolated from fetal, newborn, or adult sheep that lived at low (720 m) or at high altitude (3,801 m) for >;100 days. Blocking eNOS‐dependent NO production with 100 μM LNAME and cGMP generation by soluble guanylate cyclase with 10 μM ODQ reduced 1 μM BK vasorelaxation in fetal and newborn but not adult vessels, effects largely independent of altitude. Inhibition of PGI 2 production with 10 μM indomethacin also decreased BK‐vasorelaxation in fetal hypoxic and newborn normoxic PA. Interestingly, LTH enhanced BK‐mediated vasorelaxation in fetal vessels, suggesting a compensatory mechanism. Overall, the data imply that maturation has greater influence than altitude on eNOS ‐ cGMP mediated vasorelaxation. Moreover, cGMP as well as PGI 2 pathways are important therapeutic avenues for pulmonary hypertension in newborns and adults. (NSF MRI923559, NIH R03HD69746, R01HD31226, R01HD3807, R01HL95973, P20MD6988)