Hypoxia-Induced Contractions of Porcine Pulmonary Artery Strips Depend on Intact Endothelium

Abstract

Experiments were carried out to test the hypothesis that intact endothelium is required for hypoxia-induced contractions of pulmonary vascular muscle in vitro. To study this possibility, we cut pairs of transverse strips from main pulmonary arteries of pigs, removed the endothelium from one strip, and mounted the strips on force transducers in separate tissue baths. After an adaptation period of 4-6 h at an oxygen tension of 40 torr, strips with intact endothelium contracted spontaneously when the oxygen tension was decreased from 140 torr to near zero torr (6.5 ± 1.1 gm-wt/cm², mean ± SEM) whereas strips without endothelium contracted significantly less (1.0 ± 0.3 gm-wt/cm², p <0.001, n = 14 pairs). However, strips with and without endothelium contracted equally in response to incremental concentrations of norepinephrine. Each of several drugs (atropine, propranolol, phentolamine, or indomethacin, each 1O⁻⁵ M) had no effect on hypoxia-induced contractions when added to the bath prior to hypoxia. Similarly, a decrease in bath pH from 7.4 to 7.2 had no effect. Because we suspected that the endothelium might be releasing a mediator causing increased tone in response to hypoxia, we cleansed the bath during hypoxia, but this maneuver did not change hypoxia-induced contractions. Placing strips with intact endothelium close to strips without endothelium and measuring tension in the bath during hypoxia did not induce contractions in the strip without endothelium. We conclude that an intact endothelium is necessary for hypoxia-induced contractions in vitro in main pulmonary arteries from pigs. Although main pulmonary arteries are not primarily responsible for hypoxic vaso constriction in vivo, our findings suggest a possible role for endothelium in the pulmonary vascular response to hypoxia.