Effect of chronic hypoxia on fetal pulmonary vascular contractility

Abstract

The present study tested the hypothesis that chronic hypoxia differentially regulates contractility of fetal pulmonary arteries and veins. Fourth generation pulmonary arteries and veins were isolated from near‐term fetuses of normoxic control and chronically hypoxic (exposure to high altitude 3,801m for 110 days, PaO2: 60 Torr) pregnant ewes. Chronic hypoxia did not significantly change KCl‐induced contractions. In pulmonary arteries, chronic hypoxia significantly enhanced NE‐induced contractions, increasing the maximal response from 104.6±2.6 to 136.4±4.0 %Kmax (P<0.05). Inhibition of eNOS with L‐NNA showed no effect on NE‐induced contractions in either control or hypoxic arteries. In pulmonary veins, chronic hypoxia had no effect on NE‐induced contractions in the absence of L‐NNA. L‐NNA significantly increased NE‐induced contractions in control vessels, and this effect was significantly reduced in hypoxic vessels. In the presence of L‐NNA, chronic hypoxia significantly decreased NE‐induced contractions of pulmonary veins (217.1±10.1 vs 149.7±10.1 %Kmax, P<0.05). In addition, chronic hypoxia significantly decreased SNP‐induced relaxations of both arteries and veins. The results suggest that chronic hypoxia increases NE‐induced contractions in fetal pulmonary arteries that are not regulated by NO. In contrast, chronic hypoxia decreases both NE‐induced contractions and NO‐mediated relaxations in fetal pulmonary veins. Furthermore, chronic hypoxia decreases smooth muscle sensitivity to NO‐induced relaxations in both pulmonary arteries and veins.(Supported in part by NIH grant HD31226)