Effects of Long-Term High-Altitude Hypoxia on Ioslated Fetal Ovine Coronary Arteries

Abstract

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

Methods: Maximal contractile responses (T_max) 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, Nω-nitro-L-arginine and Nω-nitro-L-arginine ester.

Results: In high-altitude fetuses, 90 mmol/L KCl T_max 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 T_max to U46619 in the high-altitude RCA segments and augmented T_max 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.