Effects of hypoxia upon contractions evoked in isolated rabbit pulmonary artery by potassium and noradrenaline.

1. Comparisons have been made between rabbit thoracic aorta and main pulmonary artery of the effects of hypoxia upon contractions evoked by noradrenaline (NA) and KCl (K+). 2. Contractions were evoked in cylindrical sections of pulmonary artery and aorta, mounted for isometric recording of tension, by NA and K+ (at ED80) in normoxia (PO2 110 mmHg) and hypoxia (PO2 23 or 7 mmHg). Contractions were also evoked in Ca2(+)-free conditions with EGTA to prevent influx of extracellular Ca2+. All contractions are expressed as a percentage of normoxic response in the presence of Ca2+. 3. Potassium-evoked contractions of aorta and pulmonary artery were reduced to a similar extent by both levels of hypoxia, to 85 and 92% respectively. As expected K(+)-evoked contractions were virtually abolished by Ca2(+)-free conditions. It is proposed that hypoxia has a small inhibitory effect upon contraction mediated by Ca2+ influx via voltage-operated Ca2+ channels. 4. In the aorta in the presence of Ca2+, hypoxia reduced NA-evoked contractions to 84% at PO2 23 mmHg and 34% at PO2 7 mmHg. In the absence of Ca2+, NA-evoked contractions reached 73% in normoxia, but only 43 and 21% at PO2 23 and 7 mmHg respectively. These results suggest that hypoxia reduces the component of contraction that is mediated by release of intracellular Ca2+ and possibly that mediated by agonist-induced Ca2+ influx. 5. In the pulmonary artery also, NA-evoked responses in the absence of Ca2+ were reduced from 60% in normoxia, to 49 and 38% at PO2 23 and 7 mmHg. But, in the presence of Ca2+, hypoxia potentiated NA-evoked contractions to 113 and 111% at PO2 23 and 7 mmHg respectively. It is proposed that in the pulmonary artery, hypoxia reduces the component of contraction mediated by release of intracellular Ca2+, but facilitates that mediated by extracellular Ca2+. Possible mechanisms are discussed.