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Journal of the Society for Gynecologic Investigation
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Ca2+ Sensitivity of Fetal Coronary Arteries Exposed to Long-Term, High-Altitude Hypoxia

Felizabel C. Garcia, PhD

Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California; fcgarcia{at}worldnet.att.net

Virginia M. Stiffel, BS

William J. Pearce, PhD

Lubo Zhang, PhD

Raymond D. Gilbert, PhD

Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California

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 ß-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 ß-escin-permeabilized coronary artery rings, the effect of U46619 on Ca2+ sensitivity was tested.

Results: Maximum Ca2+-activated force (Tmax) 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.

Key Words: Intrauterine hypoxemia • Ca2+ sensitivity • thromboxane A2 • ß-escin

Journal of the Society for Gynecologic Investigation, Vol. 7, No. 3, 161-166 (2000)
DOI: 10.1177/107155760000700304
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