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

Abstract

Objective: To determine the contribution of decreased calcium responsiveness of fetal coronary arteries to decreased contractile responses to potassium and the thromboxane A₂ analogue U46619 in these arteries after exposure to chronic hypoxemia.

Methods: Concentration-response curves to Ca²⁺ in β-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 β-escin-permeabilized coronary artery rings, the effect of U46619 on Ca²⁺ sensitivity was tested.

Results: Maximum Ca²⁺-activated force (T_max) was decreased in HA LCx (CON 0.091 ± 0.010 versus HA 0.057 ± 0.006 g/cm²; P < .05) and HA LAD (CON 0.065 ± 0.012 versus HA 0.031 ± 0.007 g/cm²; P < .05). No significant difference was observed in the RCA. There was no change in the pD₂ (-log EC₅₀) values between CON and HA coronary rings. The Ca²⁺ sensitizing effect of U46619 on submaximal Ca²⁺-activated force was lower only in the HA LCx (CON 0.044 ± 0.010 versus HA 0.023 ± 0.006 g/cm² at 10^-5 mol/L; P < .05).

Conclusion: These results indicate that maximum tension development in response to Ca²⁺ was decreased in the HA LCx and LAD but not the RCA; however, Ca²⁺ sensitivity of the contractile apparatus was unaltered in all of them. Decreased Ca²⁺ responsiveness may partially explain the decreased contractile capability of fetal LCx and LAD during long-term, high-altitude intrauterine hypoxemia.

Keywords

Intrauterine hypoxemia Ca2+ sensitivity thromboxane A2 β-escin

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