Chronic hypoxia opposes pregnancy-induced increase in uterine artery vasodilator response to flow.
We tested the hypotheses that pregnancy increases the uterine artery (UA) vasodilator response to flow and that this increase is impaired under conditions of chronic hypoxia (30 days, simulated elevation 3,960 m). UA were isolated from 24 normoxic or chronically hypoxic midpregnant guinea pigs and studied with the use of pressure myography. Normoxic pregnancy increased UA flow vasodilator response and protected against a rise in wall shear stress (WSS). Chronic hypoxia opposed these effects, prompting vasoconstriction at high flow and increasing WSS above levels seen in normoxic pregnant UA. The nitric oxide synthase inhibitor N(G)-nitro-l-arginine (l-NNA) eliminated the pregnancy-associated increase in flow vasodilation in normoxic UA, suggesting that increased nitric oxide production was responsible. The considerable residual vasodilation after nitric oxide synthase and cyclooxygenase inhibition implicated endothelial-derived hyperpolarizing factor (EDHF) as an additional contributor to flow vasodilation. l-NNA increased flow vasodilation in UA from chronically hypoxic animals, suggesting that chronic hypoxia may have lowered EDHF or elevated peroxynitrite production. In conclusion, flow is an important physiological vasodilator for the acute and more chronic UA dimensional changes required to increase uteroplacental blood flow during normal pregnancy. Chronic hypoxia may be a mechanism that opposes the pregnancy-associated rise in UA flow vasodilation, thereby increasing the incidence of preeclampsia and intrauterine growth restriction at a high altitude.
Mateev
Stephanie
S
Women's Health Research Center and Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver 80262, USA.
Sillau
A Hugo
AH
Mouser
Rhonda
R
McCullough
Robert E
RE
White
Margueritte M
MM
Young
David A
DA
Moore
Lorna G
LG
D000531:Altitude; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology*; D001273:Atmosphere Exposure Chambers; D001783:Blood Flow Velocity / Q000502:physiology; D002908:Chronic Disease; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008469:Meclofenamic Acid / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011247:Pregnancy; D013314:Stress, Mechanical; D014599:Uterus / Q000098:blood supply*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019335:Nitroarginine; D008469:Meclofenamic Acid; D019001:Nitric Oxide Synthase