Effects of long-term high-altitude hypoxia on isolated fetal ovine coronary arteries.
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 A(2) 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, Nomega-nitro-L-arginine and Nomega-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 approximately 62% in PLCx, approximately 59% in DLCx, approximately 57% in LAD, and approximately 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).


CONCLUSIONS
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 partially explain the maintained redistribution of cardiac output to the fetal heart during exposure to long-term high-altitude hypoxia.
Garcia
F C
FC
Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California 92350, USA. fcgarcia@att.net
Stiffel
V M
VM
Gilbert
R D
RD
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000531:Altitude; D000818:Animals; D003331:Coronary Vessels / Q000196:embryology* / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D000860:Hypoxia / Q000209:etiology / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D012756:Sheep; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019001:Nitric Oxide Synthase; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester