Calcium signaling through store operated channels (SOC) is involved in hypoxic
pulmonary hypertension. We determined whether a treatment with 2-aminoethyldiphenylborinate (2-APB), a compound with SOC blocker activity, reduces
pulmonary hypertension and
vascular remodeling. Twelve newborn lambs exposed to perinatal chronic
hypoxia were studied, 6 of them received a 2-APB treatment and the other 6 received vehicle treatment, for 10 days in both cases. Throughout this period, we recorded cardiopulmonary variables and on day 11 we evaluated the response to an acute hypoxic challenge. Additionally, we assessed the
vasoconstrictor and
vasodilator function in isolated pulmonary arteries as well as their remodeling in lung slices. 2-APB reduced pulmonary arterial pressure at the third and tenth days, cardiac output between the fourth and eighth days, and pulmonary vascular resistance at the tenth day of treatment. The pulmonary
vasoconstrictor response to acute
hypoxia was reduced by the end of treatment. 2-APB also decreased maximal
vasoconstrictor response to the
thromboxane mimetic
U46619 and
endothelin-1 and increased maximal relaxation to 8-Br-cGMP. The maximal relaxation and potency to
phosphodiesterase-5 and
Rho-kinase inhibition with
sildenafil and
fasudil respectively, were also increased. Finally, 2-APB reduced the medial and adventitial layers' thickness, the expression of α-actin and the percentage of Ki67+ nuclei of small pulmonary arteries. Taken together, our results indicate that 2-APB reduces
pulmonary hypertension,
vasoconstrictor responses and pathological remodeling in pulmonary hypertensive lambs. We conclude that SOC targeting may be a useful strategy for the treatment of neonatal
pulmonary hypertension, however, further testing of specific blockers is needed.