Effects of Long-Term, High-Altitude Hypoxemia on Fetal Ovine Coronary Arteries

<p>To our knowledge, this is the first series of in vitro studies to investigate the effects of long-term, high-altitude hypoxemia on the contractility of fetal coronary vessels, namely the left circumflex, left anterior descending, and right coronary arteries. We have found that in response to chronic hypoxia, isolated fetal ovine coronary arteries exhibit attenuated contractile responsiveness to potassium and the thromboxane A2 mimetic. U46619. Furthermore, long-term, high-altitude hypoxia produced no significant alteration in the maximum relaxation response and sensitivity to adenosine in all vessel groups examined. We also addressed the possible role of nitric oxide (NO) in the pharmacological responsiveness of isolated fetal coronary artery rings to potassium. U46619, and adenosine by conducting paired studies in the absence and presence of the nitric oxide synthase (NOS) inhibitors, Nω-nitro-L-arginine (L-NNA) and Nω-nitro-Larginine ester (L-NAME). Our data suggest that basal nitric oxide production plays little if any physiological role in the reactivity of isolated fetal coronary arteries to these agonists under control and chronically hypoxic conditions. Exposure to long-term, high-altitude hypoxia resulted in decreased maximum Ca2+-activated force in B-escin permeabilized left circumflex and left anterior descending preparations. Furthermore, enhancement of Ca2+-activated force by U46619 was attenuated in the high-altitude left circumflex coronary rings. Ca2+ sensitivity of the contractile proteins; however, was unaltered by chronic hypoxia. One possible explanation for the reduction in contractility of fetal coronary arteries exposed to long-term, high-altitude hypoxia is an alteration in the extracellular matrix proteins present in the tunica medial layer of the vessels.</p> <p>Anecdotal findings from our laboratory show that vascular remodeling occurs in the tunica media layer of the coronary arteries isolated from the high-altitude fetuses. The observed decrease in contractile capabilities of the fetal coronary arteries as a result of exposure chronic hypoxia may be responsible for the maintenance of blood flow redistribution to the fetal heart. Our data suggest that changes in the structure and function of fetal coronary arteries are crucial for the adaptation to long-term, high-altitude hypoxemia.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Physiology

Year

1999

Author dc:creator

• Garcia, Felizabel C.

Contributors dc:contributor

• Raymond D. Gilbert
• John Buchholz
• Charles A. Ducsay
• William J. Pearce
• Ralph E. Purdy
• Lubo Zhang

• Physiology
• Anoxia -- embryology; Atmospheric Pressure; Oxygen; Coronary Vessels -- physiology.

Statement dc:rights

• This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/1154

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-2086