Differential effects of hypoxia upon contractions evoked by potassium and noradrenaline in rabbit arteries in vitro.

摘要

1. A study has been made on isolated sections of rabbit femoral, renal and saphenous arteries of the effects of graded hypoxia (reducing bath PO2 from 110 mmHg, normoxia, to 55, 23 and 6 mmHg) upon contractile responses evoked by noradrenaline (NA) and KCl to 80% of maximum. 2. Potassium-evoked contractions were not affected by moderate hypoxia but were reduced in all vessels to 70-80% of the control response in normoxia, by exposure to either PO2 23 or 6 mmHg. Potassium-evoked contractions were virtually abolished by Ca2(+)-free Krebs solution and greatly reduced by verapamil (10 microM), indicating that they relied upon influx of extracellular Ca2+. 3. By contrast, NA-evoked contractions were reduced in a graded fashion in all vessels by exposure to graded levels of hypoxia and at PO2 6 mmHg they were significantly more reduced than K(+)-evoked contractions. Noradrenaline-evoked contractions of femoral arteries were most affected, being reduced to 80% of control at PO2 55 mmHg, and to 28% and 6% of control at PO2 23 and 6 mmHg respectively. Contractions in renal arteries were least affected, being reduced to only 47% of control at PO2 6 mmHg. 4. Noradrenaline-evoked contractions were reduced, but not abolished, in Ca2(+)-free Krebs solution. In normoxia, they reached 42%, 35% and 25% of control responses in the presence of Ca2+ in femoral, renal and saphenous arteries respectively. The Ca2(+)-free responses of the femoral and saphenous arteries were significantly different, indicating that the femoral arteries were least dependent and saphenous most dependent on influx of extracellular Ca2+ for contraction. 5. Contractions evoked by NA in Ca2(+)-free Krebs solution were not significantly affected by PO2 55 mmHg. Those evoked in saphenous arteries were not affected by more severe hypoxia, but in renal arteries they were significantly reduced at PO2 23 mmHg, while in femoral arteries they were significantly reduced both at PO2 23 and at PO2 6 mmHg. 6. Verapamil produced changes similar to Ca2+ withdrawal. Contractions evoked by NA in the presence of verapamil were affected by hypoxia in a similar way to those evoked in the absence of Ca2+. 7. These results indicate that the inhibition of contraction induced by hypoxia is not simply dependent upon inhibition of Ca2+ influx. Instead, we propose that receptor-operated rather than voltage-operated processes are particularly vulnerable, there being inhibition of the components of contraction which are dependent on receptor-operated Ca2+ influx and release of intracellular Ca2+.