Abstract

Pregnancy at high altitude yields neonates with pulmonary hypertension (1). Therapies available today to decrease pulmonary arterial pressure (PAP) are insuffi- cient to treat an important number of human neonates. Hemin treatment in high altitude neonatal sheep showed a partial decrease in PAP (2) and a lesser smooth muscle thickness in small pulmonary arteries (3). Hypothesis: We hypothesize that the decrease in PAP after hemin-treated newborn lambs, was due partially to an increased protein expression and function of BKCa channels and an augmented protein expression and function of PKG-1.Methods: Ten lambs, whose gestation, birth and experimental procedures took place in high altitude (Putre, 3600 m), were divided in two groups. Five neonatal sheep were treated with hemin (Sigma-Aldrich Chemical, St Louis, MO, USA; 15 mg/ Kg/day, subcutaneously) for 10 days and five neonatal lambs were used as controls. After treatment, they underwent euthanasia with an overdose of sodium thiopentone (100 mgkg-1 IV) a) to study the vasoreactivity of small pulmonary artery, to a BKCa channel opener (NS 1619) and blocker (Paxilin), utilizing wire myography and b) to investigate protein expression of BKCa, PKG-1, and b-actin in total lung lysates by immunoblot with specific antibodies. Results: The vasoreactivity studies showed an increase maximal relaxation with the BKCa channel opener, between control and hemin-treated lambs (84.12 þ 4.70% vs. 60.93 þ 3.11% respectively, p < 0.05). The contraction produced by the BKCa channel blocker, was increased in the hemin-treated lambs (98.3 þ 1.9% vs. 123.9 þ 9.9%; p < 0.05). The BKCa and PKG-1 protein expression was increased in the hemin-treated lambs (1.32 þ 0.34 vs. 2.42 þ 0.24 and 1.76 þ 0.23 vs. 2.95 þ 0.81 respectively p < 0.05). Conclusions: The lower pulmonary arterial pressure in the hemin-treated newborns can be partially explained by the increased of PKG-1 and BKCa channel protein expression and an increased BKCa function. Studies are in progress to investigate further these possibilities.