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Journal of the Society for Gynecologic Investigation
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Effects of Long-Term High-Altitude Hypoxia on Ioslated Fetal Ovine Coronary Arteries

Felizabel C. Garcia, PhD

Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA 92350; fcgarcia{at}att.net

Virginia M. Stiffel, BS

Raymond D. Gilbert, PhD

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

Objective: To examine the effects of long-term high-altitude hypoxia on the contractile properties of isolated fetal coronary arteries.

Methods: Maximal contractile responses (Tmax) to 90 mmol/L KCl and the thromboxane A2 mimetic U46619 were measured in proximal (PLCx) and distal left circumflex (DLCx), left anterior descending (LAD), and right coronary arterial (RCA) rings from high-altitude and control fetuses. Paired studies were conducted with and without nitric oxide synthase (NOS) inhibitors, N{omega}-nitro-L-arginine and N{omega}-nitro-L-arginine ester.

Results: In high-altitude fetuses, 90 mmol/L KCl Tmax responses in both intact and NOS-blocked rings decreased by ~62% in PLCx, ~59% in DLCx, ~57% in LAD, and ~47% in RCA (n = 9-18/group; P < .05). High-altitude vessels also exhibited decreased sensitivity to U46619. NOS blockade potentiated Tmax to U46619 in the high-altitude RCA segments and augmented Tmax to U46619 in high-altitude RCA compared with its treated control counterpart (P < .05).

Conclusion: These results suggest that nitric oxide influences the pharmacologic responsiveness of the RCA to U46619. Furthermore, long-term high-altitude hypoxia significantly alters the contractile capabilities of fetal coronary arteries. These observations may partiall explain the maintained redistribution of cardiac output to the fetal heart during exposure to long-term high-altitude hypoxia.

Key Words: Coronary artery • thromboxane A2 • nitric oxide synthase

Journal of the Society for Gynecologic Investigation, Vol. 7, No. 4, 211-217 (2000)
DOI: 10.1177/107155760000700404
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