Neonatal hypoxia: long term effects on pulmonary arterial muscle

Abstract

The purpose of this study was to determine if neonatal hypoxia alters pulmonary arterial smooth muscle (PASM) function in young adult rats. One day old rats were made hypoxic (FI O 2 = 0.1) for 5 days, then maintained under normoxic conditions until young adulthood (45–50 days). Age-matched rats were used as controls. Body weight, hematocrit, dry lung weight, and right to left heart ratios were measured. Reactivity and/or responsiveness of rings of main right and left pulmonary artery of the adult to various agonists, including high K + (80 mM KCl), norepinephrine (NE), serotonin (5HT), adenosine (AD), and acute in in vitro hypoxic vasoconstriction were assessed. Isometric force production was normalized to calculate tissue cross-sectional area (N/cm 2). Maximum force production (P o) in response to 80 mM KCl for isolated rings from the hypoxic group was significantly less than for controls. Isometric force production in response to NE or to 5HT was also lower in the hypoxic group although the difference was significant for 5HT only when the endothelium was rendered non-functional. When the endothelium was intact, arterial rings from experimental animals relaxed at low doses of adenosine (10 −8 M to 10 −5 M), while control arterial muscle showed no response at these concentrations. The mean dose-response curve for NE from preparations with intact endothelium from experimental animals was significantly lower than that for the control animals, at least at doses greater than 10 −7M. To mimic acute hypoxic pulmonary vasoconstriction, isolated rings of the main right and left pulmonary artery were precontracted with either 30 mM KCl or 2.5 × 10 −7 M NE and then made hypoxic by lowering muscle bath P O 2 to 30–40 mmHg. In conclusion there was no difference in the hypoxic response per se between arterial rings from experimental animals and controls. However, maximum reactivity to high potassium stimulation and to norepinephrine stimulation is decreased in pulmonary arterial smooth muscle of adult animals that had been exposed to 5 days of hypoxia as neonates.