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

Abstract

The effect of chronic hypoxia (CH; 1–4 wk) on the electromechanical properties of the rat main pulmonary artery (MPA) was investigated. MPA rings obtained from rats exposed for 14 days to hypobaric (50.5 kPa) CH exhibited spontaneous and rhythmic contractions (SRCs) that were never observed in control (normoxic) rats. SRCs were unaffected by tetrodotoxin, phentolamine, BQ-123 and BQ-788, N-nitro-l-arginine methyl ester, or endothelium removal. CH depolarized smooth muscle cells from −58.8 ± 9 to −38.6 ± 5.4 mV and increased 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 μM). Moreover, depletion of intracellular Ca2+ stores with ryanodine (1–5 μM) or cyclopiazonic acid (3 μM) 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 development of right ventricle hypertrophy and disappear when this hypertrophy reaches a maximal value (after 3–4 wk of CH) suggests that SRCs may play a role in the adaptive process of the pulmonary circulation to CH.