Chronic hypoxia-induced spontaneous and rhythmic contractions in the rat main pulmonary artery

The effect of chronic hypoxia (CH; 1-4 wk) on the electromechanical propert ies of the rat main pulmonary artery (MPA) was investigated. MPA rings obta ined from rats exposed for 14 days to hypobaric (50.5 kPa) CK exhibited spo ntaneous and rhythmic contractions (SRCs) that were never observed in contr ol (normoxic) rats. SRCs were unaffected by tetrodotoxin, phentolamine, BQ- 123 and BQ-788, N-nitro-L-arginine methyl eater, or endothelium removal. CH depolarized smooth muscle cells from -58.8 +/- 9 to -38.6 +/- 5.4 mV and i ncreased the resting cytosolic Ca2+ concentration from 67.3 +/- 11.9 to 112 .5 +/- 16.4 nM. CH also induced spontaneous spikelike depolarizations. All of these effects were inhibited by external Ca2+ removal or nifedipine (1 m uM). Moreover, depletion of intracellular Ca2+ stores with ryanodine (1-5 m uM) or cyclopiazonic acid (3 muM) progressively attenuated SRCs. This study demonstrates that CH switches the MPA from a quiescent to a spontaneously active mechanical state. Finally, the fact that SRCs precede the developmen t of right ventricle hypertrophy and disappear when this hypertrophy reache s a maximal value (after 3-4 wk of CH) suggests that SRCs may play a role i n the adaptive process of the pulmonary circulation to CH.