Ca2+ Sensitivity of Fetal Coronary Arteries Exposed to Long-Term, High-Altitude Hypoxia

OBJECTIVE: To determine the contribution of decreased calcium responsiveness of fetal coronary arteries to decreased contractile responses to potassium and the thromboxane A(2) analogue U46619 in these arteries after exposure to chronic hypoxemia.

METHODS: Concentration-response curves to Ca(2+) in beta-escin-permeabilized left circumflex (LCx), left anterior descending (LAD), and right coronary artery (RCA) rings from high-altitude (HA) and control (CON) fetuses were measured. In a second set of beta-escin-permeabilized coronary artery rings, the effect of U46619 on Ca(2+) sensitivity was tested.

RESULTS: Maximum Ca(2+)-activated force (T(max)) was decreased in HA LCx (CON 0.091+/-0.010 versus HA 0.057+/-0.006 g/cm(2); P<.05) and HA LAD (CON 0.065+/-0.012 versus HA 0.031+/-0.007 g/cm(2); P <.05). No significant difference was observed in the RCA. There was no change in the pD(2) (-log EC(50)) values between CON and HA coronary rings. The Ca(2+) sensitizing effect of U46619 on submaximal Ca(2+)-activated force was lower only in the HA LCx (CON 0.044+/-0.010 versus HA 0.023+/-0.006 g/cm(2) at 10(-5) mol/L; P<.05).

CONCLUSION: These results indicate that maximum tension development in response to Ca(2+) was decreased in the HA LCx and LAD but not the RCA; however, Ca(2+) sensitivity of the contractile apparatus was unaltered in all of them. Decreased Ca(2+) responsiveness may partially explain the decreased contractile capability of fetal LCx and LAD during long-term, high-altitude intrauterine hypoxemia.